The dynamics of Rho GTPase signaling and implications for targeting cancer and the tumor microenvironment

References

• Biankin AV, Waddell N, Kassahn KS, Gingras MC, Muthuswamy LB, Johns AL, Miller DK, Wilson PJ, Patch AM, Wu J, et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012; 491:399-405; PMID:23103869; http://dx.doi.org/10.1038/nature11547
   PubMed Web of Science ®Google Scholar
• Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, et al. The somatic genomic landscape of glioblastoma. Cell 2013; 155:462-77; PMID:24120142; http://dx.doi.org/10.1016/j.cell.2013.09.034
   PubMed Web of Science ®Google Scholar
• Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al. Mutational landscape and significance across 12 major cancer types. Nature 2013; 502:333-9; PMID:24132290; http://dx.doi.org/10.1038/nature12634
   PubMed Web of Science ®Google Scholar
• Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, Davis A, Mongare MM, Gould J, Frederick DT, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 2012; 487:500-4; PMID:22763439; http://dx.doi.org/10.1038/nature11183
   PubMed Web of Science ®Google Scholar
• Fang H, Declerck YA. Targeting the tumor microenvironment: from understanding pathways to effective clinical trials. Cancer Res 2013; 73:4965-77; PMID:23913938; http://dx.doi.org/10.1158/0008-5472.CAN-13-0661
   PubMed Web of Science ®Google Scholar
• Tredan O, Galmarini CM, Patel K, Tannock IF. Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst 2007; 99:1441-54; PMID:17895480; http://dx.doi.org/10.1093/jnci/djm135
   PubMed Web of Science ®Google Scholar
• Cherfils J, Zeghouf M. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev 2013; 93:269-309; PMID:23303910; http://dx.doi.org/10.1152/physrev.00003.2012
   PubMed Web of Science ®Google Scholar
• Samarakoon R, Higgins CE, Higgins SP, Higgins PJ. Differential requirement for MEK/ERK and SMAD signaling in PAI-1 and CTGF expression in response to microtubule disruption. Cell Signal 2009; 21:986-95; PMID:19249354; http://dx.doi.org/10.1016/j.cellsig.2009.02.007
   PubMed Web of Science ®Google Scholar
• Samarakoon R, Higgins PJ. Integration of non-SMAD and SMAD signaling in TGF-beta1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells. Thromb Haemost 2008; 100:976-83; PMID:19132220
   PubMed Web of Science ®Google Scholar
• Timpson P, Jones GE, Frame MC, Brunton VG. Coordination of cell polarization and migration by the Rho family GTPases requires Src tyrosine kinase activity. Curr Biol 2001; 11:1836-46; PMID:11728306; http://dx.doi.org/10.1016/S0960-9822(01)00583-8
   PubMed Web of Science ®Google Scholar
• Tomar A, Schlaepfer DD. Focal adhesion kinase: switching between GAPs and GEFs in the regulation of cell motility. Curr Opin Cell Biol 2009; 21:676-83; PMID:19525103; http://dx.doi.org/10.1016/j.ceb.2009.05.006
   PubMed Web of Science ®Google Scholar
• Walker K, Olson MF. Targeting Ras and Rho GTPases as opportunities for cancer therapeutics. Current Opin Genet Dev 2005; 15:62-8; PMID:15661535; http://dx.doi.org/10.1016/j.gde.2004.11.001
   PubMed Web of Science ®Google Scholar
• Yoshizaki H, Ohba Y, Kurokawa K, Itoh RE, Nakamura T, Mochizuki N, Nagashima K, Matsuda M. Activity of Rho-family GTPases during cell division as visualized with FRET-based probes. J Cell Biol 2003; 162:223-32; PMID:12860967; http://dx.doi.org/10.1083/jcb.200212049
   PubMed Web of Science ®Google Scholar
• Yoshizaki H, Ohba Y, Parrini MC, Dulyaninova NG, Bresnick AR, Mochizuki N, Matsuda M. Cell type-specific regulation of RhoA activity during cytokinesis. J Biol Chem 2004; 279:44756-62; PMID:15308673; http://dx.doi.org/10.1074/jbc.M402292200
   PubMed Web of Science ®Google Scholar
• Maddox AS, Burridge K. RhoA is required for cortical retraction and rigidity during mitotic cell rounding. J Cell Biol 2003; 160:255-65; PMID:12538643; http://dx.doi.org/10.1083/jcb.200207130
   PubMed Web of Science ®Google Scholar
• Bai X, Lenhart KC, Bird KE, Suen AA, Rojas M, Kakoki M, Li F, Smithies O, Mack CP, Taylor JM. The smooth muscle-selective RhoGAP GRAF3 is a critical regulator of vascular tone and hypertension. Nature Commun 2013; 4:2910; PMID:24335996; http://dx.doi.org/10.1038/ncomms3910
   PubMed Web of Science ®Google Scholar
• Loirand G, Pacaud P. The role of Rho protein signaling in hypertension. Nature Rev Cardiol 2010; 7:637-47; PMID:20808285; http://dx.doi.org/10.1038/nrcardio.2010.136
   PubMed Web of Science ®Google Scholar
• Loirand G, Guerin P, Pacaud P. Rho kinases in cardiovascular physiology and pathophysiology. Circ Res 2006; 98:322-34; PMID:16484628; http://dx.doi.org/10.1161/01.RES.0000201960.04223.3c
   PubMed Web of Science ®Google Scholar
• Vesterinen HM, Currie GL, Carter S, Mee S, Watzlawick R, Egan KJ, Macleod MR, Sena ES. Systematic review and stratified meta-analysis of the efficacy of RhoA and Rho kinase inhibitors in animal models of ischaemic stroke. Syst Rev 2013; 2:33; PMID:23687965; http://dx.doi.org/10.1186/2046-4053-2-33
   PubMedGoogle Scholar
• Biro M, Munoz MA, Weninger W. Targeting Rho-GTPases in immune cell migration and inflammation. Br J Pharmacol 2014; 171:5491-506; PMID:24571448; http://dx.doi.org/10.1111/bph.12658
   PubMed Web of Science ®Google Scholar
• Musilli M, Nicolia V, Borrelli S, Scarpa S, Diana G. Behavioral effects of Rho GTPase modulation in a model of Alzheimer's disease. Behav Brain Res 2013; 237:223-9; PMID:23026376; http://dx.doi.org/10.1016/j.bbr.2012.09.043
   PubMed Web of Science ®Google Scholar
• Petratos S, Li QX, George AJ, Hou X, Kerr ML, Unabia SE, Hatzinisiriou I, Maksel D, Aguilar MI, Small DH. The beta-amyloid protein of Alzheimer's disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism. Brain 2008; 131:90-108; PMID:18000012; http://dx.doi.org/10.1093/brain/awm260
   PubMed Web of Science ®Google Scholar
• Dergham P, Ellezam B, Essagian C, Avedissian H, Lubell WD, McKerracher L. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22:6570-7; PMID:12151536
   PubMed Web of Science ®Google Scholar
• Hara M, Takayasu M, Watanabe K, Noda A, Takagi T, Suzuki Y, Yoshida J. Protein kinase inhibition by fasudil hydrochloride promotes neurological recovery after spinal cord injury in rats. J Neurosurg 2000; 93:94-101; PMID:10879764
   PubMed Web of Science ®Google Scholar
• Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat Med 2004; 10:712-8; PMID:15195086; http://dx.doi.org/10.1038/nm1060
   PubMed Web of Science ®Google Scholar
• Sung JK, Miao L, Calvert JW, Huang L, Louis Harkey H, Zhang JH. A possible role of RhoA/Rho-kinase in experimental spinal cord injury in rat. Brain Res 2003; 959:29-38; PMID:12480155; http://dx.doi.org/10.1016/S0006-8993(02)03717-4
   PubMed Web of Science ®Google Scholar
• Shibuya M, Suzuki Y, Sugita K, Saito I, Sasaki T, Takakura K, Nagata I, Kikuchi H, Takemae T, Hidaka H, et al. Effect of AT877 on cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Results of a prospective placebo-controlled double-blind trial. J Neurosurg 1992; 76:571-7; PMID:1545249; http://dx.doi.org/10.3171/jns.1992.76.4.0571
   PubMed Web of Science ®Google Scholar
• Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, Bamford M, Panchal T, Grygielko E, Wright LL, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther 2007; 320:89-98; PMID:17018693; http://dx.doi.org/10.1124/jpet.106.110635
   PubMed Web of Science ®Google Scholar
• Stavenger RA, Cui H, Dowdell SE, Franz RG, Gaitanopoulos DE, Goodman KB, Hilfiker MA, Ivy RL, Leber JD, Marino JP Jr, et al. Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high kinase selectivity and antihypertensive activity. J Med Chem 2007; 50:2-5; PMID:17201404; http://dx.doi.org/10.1021/jm060873p
   PubMed Web of Science ®Google Scholar
• Sahai E, Marshall CJ. RHO-GTPases and cancer. Nat Rev Cancer 2002; 2:133-42; PMID:12635176; http://dx.doi.org/10.1038/nrc725
   PubMed Web of Science ®Google Scholar
• Fritz G, Brachetti C, Bahlmann F, Schmidt M, Kaina B. Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer 2002; 87:635-44; PMID:12237774; http://dx.doi.org/10.1038/sj.bjc.6600510
   PubMed Web of Science ®Google Scholar
• Lane J, Martin TA, Watkins G, Mansel RE, Jiang WG. The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer. Int J Oncol 2008; 33:585-93; PMID:18695890
   PubMed Web of Science ®Google Scholar
• Liu S, Goldstein RH, Scepansky EM, Rosenblatt M. Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res 2009; 69:8742-51; PMID:19887617; http://dx.doi.org/10.1158/0008-5472.CAN-09-1541
   PubMed Web of Science ®Google Scholar
• Li NF, Gemenetzidis E, Marshall FJ, Davies D, Yu Y, Frese K, Froeling FE, Woolf AK, Feakins RM, Naito Y, et al. RhoC interacts with integrin alpha5beta1 and enhances its trafficking in migrating pancreatic carcinoma cells. PLoS One 2013; 8:e81575; PMID:24312560; http://dx.doi.org/10.1371/journal.pone.0081575
   PubMed Web of Science ®Google Scholar
• Rosenthal DT, Iyer H, Escudero S, Bao L, Wu Z, Ventura AC, Kleer CG, Arruda EM, Garikipati K, Merajver SD. p38gamma promotes breast cancer cell motility and metastasis through regulation of RhoC GTPase, cytoskeletal architecture, and a novel leading edge behavior. Cancer Res 2011; 71:6338-49; PMID:21862636; http://dx.doi.org/10.1158/0008-5472.CAN-11-1291
   PubMed Web of Science ®Google Scholar
• Wang Y, Lei R, Zhuang X, Zhang N, Pan H, Li G, Hu J, Pan X, Tao Q, Fu D, et al. DLC1-dependent parathyroid hormone-like hormone inhibition suppresses breast cancer bone metastasis. J Clin Invest 2014; 124:1646-59; PMID:24590291; http://dx.doi.org/10.1172/JCI71812
   PubMed Web of Science ®Google Scholar
• Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, Yoneda T, Mundy GR. Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest 1996; 98:1544-9; PMID:8833902; http://dx.doi.org/10.1172/JCI118947
   PubMed Web of Science ®Google Scholar
• Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 2001; 29:117-29; PMID:11586292; http://dx.doi.org/10.1038/ng1001-117
   PubMed Web of Science ®Google Scholar
• Kaneko K, Satoh K, Masamune A, Satoh A, Shimosegawa T. Expression of ROCK-1 in human pancreatic cancer: its down-regulation by morpholino oligo antisense can reduce the migration of pancreatic cancer cells in vitro. Pancreas 2002; 24:251-7; PMID:11893932; http://dx.doi.org/10.1097/00006676-200204000-00007
   PubMed Web of Science ®Google Scholar
• Kamai T, Yamanishi T, Shirataki H, Takagi K, Asami H, Ito Y, Yoshida K. Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer. Clin Cancer Res 2004; 10:4799-805; PMID:15269155; http://dx.doi.org/10.1158/1078-0432.CCR-0436-03
   PubMed Web of Science ®Google Scholar
• Samuel MS, Lopez JI, McGhee EJ, Croft DR, Strachan D, Timpson P, Munro J, Schroder E, Zhou J, Brunton VG, et al. Actomyosin-mediated cellular tension drives increased tissue stiffness and beta-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell 2011; 19:776-91; PMID:21665151; http://dx.doi.org/10.1016/j.ccr.2011.05.008
   PubMed Web of Science ®Google Scholar
• Bellovin DI, Simpson KJ, Danilov T, Maynard E, Rimm DL, Oettgen P, Mercurio AM. Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma. Oncogene 2006; 25:6959-67; PMID:16715134; http://dx.doi.org/10.1038/sj.onc.1209682
   PubMed Web of Science ®Google Scholar
• Shepelev MV, Korobko IV. The RHOV gene is overexpressed in human non-small cell lung cancer. Cancer Genet 2013; 206:393-7; PMID:24388711; http://dx.doi.org/10.1016/j.cancergen.2013.10.006
   PubMed Web of Science ®Google Scholar
• Zhao Y, Zheng HC, Chen S, Gou WF, Xiao LJ, Niu ZF. The role of RhoC in ovarian epithelial carcinoma: a marker for carcinogenesis, progression, prognosis, and target therapy. Gynecol Oncol 2013; 130:570-8; PMID:23764197; http://dx.doi.org/10.1016/j.ygyno.2013.06.004
   PubMed Web of Science ®Google Scholar
• Yoshioka K, Nakamori S, Itoh K. Overexpression of small GTP-binding protein RhoA promotes invasion of tumor cells. Cancer Res 1999; 59:2004-10; PMID:10213513
   PubMed Web of Science ®Google Scholar
• Bray K, Gillette M, Young J, Loughran E, Hwang M, Sears JC, Vargo-Gogola T. Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration. Breast Cancer Res 2013; 15:R91; PMID:24074261; http://dx.doi.org/10.1186/bcr3487
   PubMed Web of Science ®Google Scholar
• Parri M, Chiarugi P. Rac and Rho GTPases in cancer cell motility control. Cell Commun Signal 2010; 8:23; PMID:20822528; http://dx.doi.org/10.1186/1478-811X-8-23
   PubMed Web of Science ®Google Scholar
• Sahai E, Marshall CJ. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat Cell Biol 2003; 5:711-9; PMID:12844144; http://dx.doi.org/10.1038/ncb1019
   PubMed Web of Science ®Google Scholar
• Yamazaki D, Kurisu S, Takenawa T. Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates. Oncogene 2009; 28:1570-83; PMID:19234490; http://dx.doi.org/10.1038/onc.2009.2
   PubMed Web of Science ®Google Scholar
• Guo X, Wang M, Jiang J, Xie C, Peng F, Li X, Tian R, Qin R. Balanced Tiam1-rac1 and RhoA drives proliferation and invasion of pancreatic cancer cells. Mol Cancer Res 2013; 11:230-9; PMID:23322732; http://dx.doi.org/10.1158/1541-7786.MCR-12-0632
   PubMed Web of Science ®Google Scholar
• de Toledo M, Anguille C, Roger L, Roux P, Gadea G. Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity. PLoS One 2012; 7:e48344; PMID:23144867; http://dx.doi.org/10.1371/journal.pone.0048344
   PubMed Web of Science ®Google Scholar
• Coleman ML, Marshall CJ, Olson MF. RAS and RHO GTPases in G1-phase cell-cycle regulation. Nat Rev Mol Cell Biol 2004; 5:355-66; PMID:15122349; http://dx.doi.org/10.1038/nrm1365
   PubMed Web of Science ®Google Scholar
• Boerner JL, Danielsen A, McManus MJ, Maihle NJ. Activation of Rho is required for ligand-independent oncogenic signaling by a mutant epidermal growth factor receptor. J Biol Chem 2001; 276:3691-5; PMID:11110781; http://dx.doi.org/10.1074/jbc.M003801200
   PubMed Web of Science ®Google Scholar
• Servitja JM, Marinissen MJ, Sodhi A, Bustelo XR, Gutkind JS. Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src. J Biol Chem 2003; 278:34339-46; PMID:12810717; http://dx.doi.org/10.1074/jbc.M302960200
   PubMed Web of Science ®Google Scholar
• Wu WJ, Tu S, Cerione RA. Activated Cdc42 sequesters c-Cbl and prevents EGF receptor degradation. Cell 2003; 114:715-25; PMID:14505571; http://dx.doi.org/10.1016/S0092-8674(03)00688-3
   PubMed Web of Science ®Google Scholar
• Kim C, Yang H, Fukushima Y, Saw PE, Lee J, Park JS, Park I, Jung J, Kataoka H, Lee D, et al. Vascular RhoJ is an effective and selective target for tumor angiogenesis and vascular disruption. Cancer Cell 2014; 25:102-17; PMID:24434213; http://dx.doi.org/10.1016/j.ccr.2013.12.010
   PubMed Web of Science ®Google Scholar
• Ho H, Aruri J, Kapadia R, Mehr H, White MA, Ganesan AK. RhoJ regulates melanoma chemoresistance by suppressing pathways that sense DNA damage. Cancer Res 2012; 72:5516-28; PMID:22971344; http://dx.doi.org/10.1158/0008-5472.CAN-12-0775
   PubMed Web of Science ®Google Scholar
• Hofbauer SW, Krenn PW, Ganghammer S, Asslaber D, Pichler U, Oberascher K, Henschler R, Wallner M, Kerschbaum H, Greil R, et al. Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells. Blood 2014; 123:2181-8; PMID:24501217; http://dx.doi.org/10.1182/blood-2013-08-523563
   PubMed Web of Science ®Google Scholar
• Montresor A, Bolomini-Vittori M, Toffali L, Rossi B, Constantin G, Laudanna C. JAK tyrosine kinases promote hierarchical activation of Rho and Rap modules of integrin activation. J Cell Biol 2013; 203:1003-19; PMID:24368807; http://dx.doi.org/10.1083/jcb.201303067
   PubMed Web of Science ®Google Scholar
• Raptis L, Arulanandam R, Geletu M, Turkson J. The R(h)oads to Stat3: Stat3 activation by the Rho GTPases. Exp Cell Res 2011; 317:1787-95; PMID:21619876; http://dx.doi.org/10.1016/j.yexcr.2011.05.008
   PubMed Web of Science ®Google Scholar
• Kawasaki Y, Senda T, Ishidate T, Koyama R, Morishita T, Iwayama Y, Higuchi O, Akiyama T. Asef, a link between the tumor suppressor APC and G-protein signaling. Science 2000; 289:1194-7; PMID:10947987; http://dx.doi.org/10.1126/science.289.5482.1194
   PubMed Web of Science ®Google Scholar
• Sandilands E, Cans C, Fincham VJ, Brunton VG, Mellor H, Prendergast GC, Norman JC, Superti-Furga G, Frame MC. RhoB and actin polymerization coordinate Src activation with endosome-mediated delivery to the membrane. Dev Cell 2004; 7:855-69; PMID:15572128; http://dx.doi.org/10.1016/j.devcel.2004.09.019
   PubMed Web of Science ®Google Scholar
• Machesky LM, Sansom OJ. Rac1 in the driver's seat for melanoma. Pigment Cell Melanoma Res 2012; 25:762-4; PMID:22882909; http://dx.doi.org/10.1111/pcmr.12004
   PubMed Web of Science ®Google Scholar
• Orgaz JL, Herraiz C, Sanz-Moreno V. Rho GTPases modulate malignant transformation of tumor cells. Small GTPases 2014; 5:e29019; PMID:25036871; http://dx.doi.org/10.4161/sgtp.29019
   PubMedGoogle Scholar
• Eva A, Aaronson SA. Isolation of a new human oncogene from a diffuse B-cell lymphoma. Nature 1985; 316:273-5; PMID:3875039; http://dx.doi.org/10.1038/316273a0
   PubMed Web of Science ®Google Scholar
• Katzav S, Martin-Zanca D, Barbacid M. vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells. EMBO J 1989; 8:2283-90; PMID:2477241
   PubMed Web of Science ®Google Scholar
• Montero JC, Seoane S, Ocana A, Pandiella A. P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer. Oncogene 2011; 30:1059-71; PMID:21042280; http://dx.doi.org/10.1038/onc.2010.489
   PubMed Web of Science ®Google Scholar
• Toksoz D, Williams DA. Novel human oncogene lbc detected by transfection with distinct homology regions to signal transduction products. Oncogene 1994; 9:621-8; PMID:8290273
   PubMed Web of Science ®Google Scholar
• Jaiswal M, Dvorsky R, Amin E, Risse SL, Fansa EK, Zhang SC, Taha MS, Gauhar AR, Nakhaei-Rad S, Kordes C, et al. Functional cross-talk between ras and rho pathways: a Ras-specific GTPase-activating protein (p120RasGAP) competitively inhibits the RhoGAP activity of deleted in liver cancer (DLC) tumor suppressor by masking the catalytic arginine finger. J Biol Chem 2014; 289:6839-49; PMID:24443565
   PubMed Web of Science ®Google Scholar
• Radu M, Rawat SJ, Beeser A, Iliuk A, Tao WA, Chernoff J. ArhGAP15, a Rac-specific GTPase-activating protein, plays a dual role in inhibiting small GTPase signaling. J Biol Chem 2013; 288:21117-25; PMID:23760270; http://dx.doi.org/10.1074/jbc.M113.459719
   PubMed Web of Science ®Google Scholar
• Barone I, Brusco L, Gu G, Selever J, Beyer A, Covington KR, Tsimelzon A, Wang T, Hilsenbeck SG, Chamness GC, et al. Loss of Rho GDIalpha and resistance to tamoxifen via effects on estrogen receptor alpha. J Natl Cancer Inst 2011; 103:538-52; PMID:21447808; http://dx.doi.org/10.1093/jnci/djr058
   PubMed Web of Science ®Google Scholar
• Cho HJ, Baek KE, Kim IK, Park SM, Choi YL, Nam IK, Park SH, Im MJ, Yoo JM, Ryu KJ, et al. Proteomics-based strategy to delineate the molecular mechanisms of RhoGDI2-induced metastasis and drug resistance in gastric cancer. J Proteome Res 2012; 11:2355-64; PMID:22364609; http://dx.doi.org/10.1021/pr2011186
   PubMed Web of Science ®Google Scholar
• Wu Y, Moissoglu K, Wang H, Wang X, Frierson HF, Schwartz MA, Theodorescu D. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proc Natl Acad Sci U S A 2009; 106:5807-12; PMID:19321744; http://dx.doi.org/10.1073/pnas.0810094106
   PubMed Web of Science ®Google Scholar
• Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001; 412:341-6; PMID:11460166; http://dx.doi.org/10.1038/35085588
   PubMed Web of Science ®Google Scholar
• Preudhomme C, Roumier C, Hildebrand MP, Dallery-Prudhomme E, Lantoine D, Lai JL, Daudignon A, Adenis C, Bauters F, Fenaux P, et al. Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma. Oncogene 2000; 19:2023-32; PMID:10803463; http://dx.doi.org/10.1038/sj.onc.1203521
   PubMed Web of Science ®Google Scholar
• Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, Muto H, Tsuyama N, Sato-Otsubo A, Okuno Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet 2014; 46:171-5; PMID:24413737; http://dx.doi.org/10.1038/ng.2872
   PubMed Web of Science ®Google Scholar
• Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, Kim SC, Lee B, Rho K, Lee JE, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet 2014; 46:371-5; PMID:24584070; http://dx.doi.org/10.1038/ng.2916
   PubMed Web of Science ®Google Scholar
• Federico M, Rudiger T, Bellei M, Nathwani BN, Luminari S, Coiffier B, Harris NL, Jaffe ES, Pileri SA, Savage KJ, et al. Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol 2013; 31:240-6; PMID:22869878; http://dx.doi.org/10.1200/JCO.2011.37.3647
   PubMed Web of Science ®Google Scholar
• Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014; 513:202-9; PMID:25079317; http://dx.doi.org/10.1038/nature13480
   PubMed Web of Science ®Google Scholar
• Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 2012; 44:1006-14; PMID:22842228; http://dx.doi.org/10.1038/ng.2359
   PubMed Web of Science ®Google Scholar
• Davis MJ, Ha BH, Holman EC, Halaban R, Schlessinger J, Boggon TJ. RAC1P29S is a spontaneously activating cancer-associated GTPase. Proc Natl Acad Sci U S A 2013; 110:912-7; PMID:23284172; http://dx.doi.org/10.1073/pnas.1220895110
   PubMed Web of Science ®Google Scholar
• Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, et al. A landscape of driver mutations in melanoma. Cell 2012; 150:251-63; PMID:22817889; http://dx.doi.org/10.1016/j.cell.2012.06.024
   PubMed Web of Science ®Google Scholar
• Matos P, Oliveira C, Velho S, Goncalves V, da Costa LT, Moyer MP, Seruca R, Jordan P. B-Raf(V600E) cooperates with alternative spliced Rac1b to sustain colorectal cancer cell survival. Gastroenterology 2008; 135:899-906; PMID:18602919; http://dx.doi.org/10.1053/j.gastro.2008.05.052
   PubMed Web of Science ®Google Scholar
• Kraynov VS, Chamberlain C, Bokoch GM, Schwartz MA, Slabaugh S, Hahn KM. Localized Rac activation dynamics visualized in living cells. Science 2000; 290:333-7; PMID:11030651; http://dx.doi.org/10.1126/science.290.5490.333
   PubMed Web of Science ®Google Scholar
• Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM, Danuser G. Coordination of Rho GTPase activities during cell protrusion. Nature 2009; 461:99-103; PMID:19693013; http://dx.doi.org/10.1038/nature08242
   PubMed Web of Science ®Google Scholar
• Pertz O, Hodgson L, Klemke RL, Hahn KM. Spatiotemporal dynamics of RhoA activity in migrating cells. Nature 2006; 440:1069-72; PMID:16547516; http://dx.doi.org/10.1038/nature04665
   PubMed Web of Science ®Google Scholar
• Timpson P, McGhee EJ, Morton JP, von Kriegsheim A, Schwarz JP, Karim SA, Doyle B, Quinn JA, Carragher NO, Edward M, et al. Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53. Cancer Res 2011; 71:747-57; PMID:21266354; http://dx.doi.org/10.1158/0008-5472.CAN-10-2267
   PubMed Web of Science ®Google Scholar
• Fernandez-Espartero CH, Ramel D, Farago M, Malartre M, Luque CM, Limanovich S, Katzav S, Emery G, Martin-Bermudo MD. GTP exchange factor Vav regulates guided cell migration by coupling guidance receptor signalling to local Rac activation. J Cell Sci 2013; 126:2285-93; PMID:23525006; http://dx.doi.org/10.1242/jcs.124438
   PubMed Web of Science ®Google Scholar
• Stramer B, Wood W, Galko MJ, Redd MJ, Jacinto A, Parkhurst SM, Martin P. Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration. J Cell Biol 2005; 168:567-73; PMID:15699212; http://dx.doi.org/10.1083/jcb.200405120
   PubMed Web of Science ®Google Scholar
• Kardash E, Reichman-Fried M, Maitre JL, Boldajipour B, Papusheva E, Messerschmidt EM, Heisenberg CP, Raz E. A role for Rho GTPases and cell-cell adhesion in single-cell motility in vivo. Nat Cell Biol 2010; 12:47-53; sup pp 1-11; PMID:20010816; http://dx.doi.org/10.1038/ncb2003
   PubMed Web of Science ®Google Scholar
• Xu H, Kardash E, Chen S, Raz E, Lin F. Gbetagamma signaling controls the polarization of zebrafish primordial germ cells by regulating Rac activity. Development 2012; 139:57-62; PMID:22096073; http://dx.doi.org/10.1242/dev.073924
   PubMed Web of Science ®Google Scholar
• Hirata E, Yukinaga H, Kamioka Y, Arakawa Y, Miyamoto S, Okada T, Sahai E, Matsuda M. In vivo fluorescence resonance energy transfer imaging reveals differential activation of Rho-family GTPases in glioblastoma cell invasion. J Cell Sci 2012; 125:858-68; PMID:22399802; http://dx.doi.org/10.1242/jcs.089995
   PubMed Web of Science ®Google Scholar
• Johnsson AK, Dai Y, Nobis M, Baker MJ, McGhee EJ, Walker S, Schwarz JP, Kadir S, Morton JP, Myant KB, et al. The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues. Cell Rep 2014; 6:1153-64; PMID:24630994; http://dx.doi.org/10.1016/j.celrep.2014.02.024
   PubMed Web of Science ®Google Scholar
• Karim SA, Creedon H, Patel H, Carragher NO, Morton JP, Muller WJ, Evans TR, Gusterson B, Sansom OJ, Brunton VG. Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. J Pathol 2013; 230:430-40; PMID:23616343; http://dx.doi.org/10.1002/path.4202
   PubMed Web of Science ®Google Scholar
• Morton JP, Karim SA, Graham K, Timpson P, Jamieson N, Athineos D, Doyle B, McKay C, Heung MY, Oien KA, et al. Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology 2010; 139:292-303; PMID:20303350; http://dx.doi.org/10.1053/j.gastro.2010.03.034
   PubMed Web of Science ®Google Scholar
• Jacobetz MA, Chan DS, Neesse A, Bapiro TE, Cook N, Frese KK, Feig C, Nakagawa T, Caldwell ME, Zecchini HI, et al. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 2013; 62:112-20; PMID:22466618; http://dx.doi.org/10.1136/gutjnl-2012-302529
   PubMed Web of Science ®Google Scholar
• Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, et al. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324:1457-61; PMID:19460966; http://dx.doi.org/10.1126/science.1171362
   PubMed Web of Science ®Google Scholar
• Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell 2012; 21:418-29; PMID:22439937; http://dx.doi.org/10.1016/j.ccr.2012.01.007
   PubMed Web of Science ®Google Scholar
• Kamioka Y, Sumiyama K, Mizuno R, Matsuda M. Live imaging of transgenic mice expressing FRET biosensors. Conf Proc IEEE Eng Med Biol Soc 2013; 2013:125-8; PMID:24109640
   PubMedGoogle Scholar
• Conway JRW, Carragher NO, Timpson P. Developments in preclinical cancer imaging: innovating the discovery of therapeutics. Nat Rev Cancer 2014; 14:314-28; PMID:24739578; http://dx.doi.org/10.1038/nrc3724
   PubMed Web of Science ®Google Scholar
• Goto A, Sumiyama K, Kamioka Y, Nakasyo E, Ito K, Iwasaki M, Enomoto H, Matsuda M. GDNF and endothelin 3 regulate migration of enteric neural crest-derived cells via protein kinase A and Rac1. J Neurosci 2013; 33:4901-12; PMID:23486961; http://dx.doi.org/10.1523/JNEUROSCI.4828-12.2013
   PubMed Web of Science ®Google Scholar
• Myant KB, Cammareri P, McGhee EJ, Ridgway RA, Huels DJ, Cordero JB, Schwitalla S, Kalna G, Ogg EL, Athineos D, et al. ROS production and NF-kappaB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell 2013; 12:761-73; PMID:23665120; http://dx.doi.org/10.1016/j.stem.2013.04.006
   PubMed Web of Science ®Google Scholar
• Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007; 449:1003-7; PMID:17934449; http://dx.doi.org/10.1038/nature06196
   PubMed Web of Science ®Google Scholar
• Lindsay CR, Lawn S, Campbell AD, Faller WJ, Rambow F, Mort RL, Timpson P, Li A, Cammareri P, Ridgway RA, et al. P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nat Commun 2011; 2:555; PMID:22109529; http://dx.doi.org/10.1038/ncomms1560
   PubMed Web of Science ®Google Scholar
• Shimizu Y, Thumkeo D, Keel J, Ishizaki T, Oshima H, Oshima M, Noda Y, Matsumura F, Taketo MM, Narumiya S. ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. J Cell Biol 2005; 168:941-53; PMID:15753128; http://dx.doi.org/10.1083/jcb.200411179
   PubMed Web of Science ®Google Scholar
• Thumkeo D, Keel J, Ishizaki T, Hirose M, Nonomura K, Oshima H, Oshima M, Taketo MM, Narumiya S. Targeted disruption of the mouse rho-associated kinase 2 gene results in intrauterine growth retardation and fetal death. Mol Cell Biol 2003; 23:5043-55; PMID:12832488; http://dx.doi.org/10.1128/MCB.23.14.5043-5055.2003
   PubMed Web of Science ®Google Scholar
• Gao Y, Dickerson JB, Guo F, Zheng J, Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci U S A 2004; 101:7618-23; PMID:15128949; http://dx.doi.org/10.1073/pnas.0307512101
   PubMed Web of Science ®Google Scholar
• Shutes A, Onesto C, Picard V, Leblond B, Schweighoffer F, Der CJ. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J Biol Chem 2007; 282:35666-78; PMID:17932039; http://dx.doi.org/10.1074/jbc.M703571200
   PubMed Web of Science ®Google Scholar
• Rosenblatt AE, Garcia MI, Lyons L, Xie Y, Maiorino C, Desire L, Slingerland J, Burnstein KL. Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer. Endocr Relat Cancer 2011; 18:207-19; PMID:21118977
   PubMed Web of Science ®Google Scholar
• Zins K, Gunawardhana S, Lucas T, Abraham D, Aharinejad S. Targeting Cdc42 with the small molecule drug AZA197 suppresses primary colon cancer growth and prolongs survival in a preclinical mouse xenograft model by downregulation of PAK1 activity. J Transl Med 2013; 11:295; PMID:24279335; http://dx.doi.org/10.1186/1479-5876-11-295
   PubMed Web of Science ®Google Scholar
• Yang X, Di J, Zhang Y, Zhang S, Lu J, Liu J, Shi W. The Rho-kinase inhibitor inhibits proliferation and metastasis of small cell lung cancer. Biomed Pharmacother 2012; 66:221-7; PMID:22425182; http://dx.doi.org/10.1016/j.biopha.2011.11.011
   PubMed Web of Science ®Google Scholar
• Zhang C, Zhang S, Zhang Z, He J, Xu Y, Liu S. ROCK has a crucial role in regulating prostate tumor growth through interaction with c-Myc. Oncogene 2013; 33:5582-91; PMID:24317511; http://dx.doi.org/10.1038/onc.2013.505
   PubMed Web of Science ®Google Scholar
• Kumar MS, Hancock DC, Molina-Arcas M, Steckel M, East P, Diefenbacher M, Armenteros-Monterroso E, Lassailly F, Matthews N, Nye E, et al. The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer. Cell 2012; 149:642-55; PMID:22541434; http://dx.doi.org/10.1016/j.cell.2012.02.059
   PubMed Web of Science ®Google Scholar
• Nakabayashi H, Shimizu K. HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho-ROCK and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signal pathways. Cancer Sci 2011; 102:393-9; PMID:21166955; http://dx.doi.org/10.1111/j.1349-7006.2010.01794.x
   PubMed Web of Science ®Google Scholar
• Wozniak MA, Desai R, Solski PA, Der CJ, Keely PJ. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J Cell Biol 2003; 163:583-95; PMID:14610060; http://dx.doi.org/10.1083/jcb.200305010
   PubMed Web of Science ®Google Scholar
• Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ. Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1998; 7:1133-44; PMID:9865433
   PubMed Web of Science ®Google Scholar
• Lisanti MP, Tsirigos A, Pavlides S, Reeves KJ, Peiris-Pages M, Chadwick AL, Sanchez-Alvarez R, Lamb R, Howell A, Martinez-Outschoorn UE, et al. JNK1 stress signaling is hyper-activated in high breast density and the tumor stroma: connecting fibrosis, inflammation, and stemness for cancer prevention. Cell Cycle 2014; 13:580-99; PMID:24434780; http://dx.doi.org/10.4161/cc.27379
   PubMed Web of Science ®Google Scholar
• Ponik SM, Trier SM, Wozniak MA, Eliceiri KW, Keely PJ. RhoA is down-regulated at cell-cell contacts via p190RhoGAP-B in response to tensional homeostasis. Mol Biol Cell 2013; 24:1688-99; S1-3; PMID:23552690; http://dx.doi.org/10.1091/mbc.E12-05-0386
   PubMed Web of Science ®Google Scholar
• Croft DR, Sahai E, Mavria G, Li S, Tsai J, Lee WM, Marshall CJ, Olson MF. Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis. Cancer Res 2004; 64:8994-9001; PMID:15604264; http://dx.doi.org/10.1158/0008-5472.CAN-04-2052
   PubMed Web of Science ®Google Scholar
• Cicchi R, Kapsokalyvas D, De Giorgi V, Maio V, Van Wiechen A, Massi D, Lotti T, Pavone FS. Scoring of collagen organization in healthy and diseased human dermis by multiphoton microscopy. J Biophotonics 2010; 3:34-43; PMID:19771581; http://dx.doi.org/10.1002/jbio.200910062
   PubMed Web of Science ®Google Scholar
• Timpson P, McGhee EJ, Erami Z, Nobis M, Quinn JA, Edward M, Anderson KI. Organotypic collagen I assay: a malleable platform to assess cell behaviour in a 3-dimensional context. J Vis Exp 2011, (56):e3089; PMID:22025017; http://dx.doi.org/10.3791/3089
   PubMed Web of Science ®Google Scholar
• Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K, Sahai E. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol 2007; 9:1392-400; PMID:18037882; http://dx.doi.org/10.1038/ncb1658
   PubMed Web of Science ®Google Scholar
• Yamamoto M, Quantock AJ, Young RD, Okumura N, Ueno M, Sakamoto Y, Kinoshita S, Koizumi N. A selective inhibitor of the Rho kinase pathway, Y-27632, and its influence on wound healing in the corneal stroma. Mol Vis 2012; 18:1727-39; PMID:22815626
   PubMed Web of Science ®Google Scholar
• Rath N, Olson MF. Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy. EMBO Rep 2012; 13:900-8; PMID:22964758; http://dx.doi.org/10.1038/embor.2012.127
   PubMed Web of Science ®Google Scholar
• Brownfield DG, Venugopalan G, Lo A, Mori H, Tanner K, Fletcher DA, Bissell MJ. Patterned collagen fibers orient branching mammary epithelium through distinct signaling modules. Curr Biol 2013; 23:703-9; PMID:23562267; http://dx.doi.org/10.1016/j.cub.2013.03.032
   PubMed Web of Science ®Google Scholar
• Scott RW, Hooper S, Crighton D, Li A, Konig I, Munro J, Trivier E, Wickman G, Morin P, Croft DR, et al. LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells. J Cell Biol 2010; 191:169-85; PMID:20876278; http://dx.doi.org/10.1083/jcb.201002041
   PubMed Web of Science ®Google Scholar
• Sanz-Moreno V, Gaggioli C, Yeo M, Albrengues J, Wallberg F, Viros A, Hooper S, Mitter R, Feral CC, Cook M, et al. ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma. Cancer Cell 2011; 20:229-45; PMID:21840487; http://dx.doi.org/10.1016/j.ccr.2011.06.018
   PubMed Web of Science ®Google Scholar
• Cadamuro M, Nardo G, Indraccolo S, Dall'olmo L, Sambado L, Moserle L, Franceschet I, Colledan M, Massani M, Stecca T, et al. Platelet-derived growth factor-D and Rho GTPases regulate recruitment of cancer-associated fibroblasts in cholangiocarcinoma. Hepatology 2013; 58:1042-53; PMID:23505219; http://dx.doi.org/10.1002/hep.26384
   PubMed Web of Science ®Google Scholar
• Goicoechea SM, Garcia-Mata R, Staub J, Valdivia A, Sharek L, McCulloch CG, Hwang RF, Urrutia R, Yeh JJ, Kim HJ, et al. Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts. Oncogene 2014; 33:1265-73; PMID:23524582; http://dx.doi.org/10.1038/onc.2013.68
   PubMed Web of Science ®Google Scholar
• Brown M, Roulson JA, Hart CA, Tawadros T, Clarke NW. Arachidonic acid induction of Rho-mediated transendothelial migration in prostate cancer. Br J Cancer 2014; 110:2099-108; PMID:24595005; http://dx.doi.org/10.1038/bjc.2014.99
   PubMed Web of Science ®Google Scholar
• Reymond N, Im JH, Garg R, Vega FM, Borda d'Agua B, Riou P, Cox S, Valderrama F, Muschel RJ, Ridley AJ. Cdc42 promotes transendothelial migration of cancer cells through beta1 integrin. J Cell Biol 2012; 199:653-68; PMID:23148235; http://dx.doi.org/10.1083/jcb.201205169
   PubMed Web of Science ®Google Scholar
• Caspani EM, Crossley PH, Redondo-Garcia C, Martinez S. Glioblastoma: a pathogenic crosstalk between tumor cells and pericytes. PLoS One 2014; 9:e101402; PMID:25032689; http://dx.doi.org/10.1371/journal.pone.0101402
   PubMed Web of Science ®Google Scholar
• Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, et al. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature 2010; 465:483-6; PMID:20445537; http://dx.doi.org/10.1038/nature09002
   PubMed Web of Science ®Google Scholar
• Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 2004; 303:848-51; PMID:14764882; http://dx.doi.org/10.1126/science.1090922
   PubMed Web of Science ®Google Scholar
• Cheng N, Bhowmick NA, Chytil A, Gorksa AE, Brown KA, Muraoka R, Arteaga CL, Neilson EG, Hayward SW, Moses HL. Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Oncogene 2005; 24:5053-68; PMID:15856015; http://dx.doi.org/10.1038/sj.onc.1208685
   PubMed Web of Science ®Google Scholar
• Cheng N, Chytil A, Shyr Y, Joly A, Moses HL. Enhanced hepatocyte growth factor signaling by type II transforming growth factor-beta receptor knockout fibroblasts promotes mammary tumorigenesis. Cancer Res 2007; 67:4869-77; PMID:17495323; http://dx.doi.org/10.1158/0008-5472.CAN-06-3381
   PubMed Web of Science ®Google Scholar
• Alva JA, Zovein AC, Monvoisin A, Murphy T, Salazar A, Harvey NL, Carmeliet P, Iruela-Arispe ML. VE-Cadherin-Cre-recombinase transgenic mouse: a tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn 2006; 235:759-67; PMID:16450386; http://dx.doi.org/10.1002/dvdy.20643
   PubMed Web of Science ®Google Scholar
• Gustafsson E, Brakebusch C, Hietanen K, Fassler R. Tie-1-directed expression of Cre recombinase in endothelial cells of embryoid bodies and transgenic mice. J Cell Sci 2001; 114:671-6; PMID:11171372
   PubMed Web of Science ®Google Scholar
• Kisanuki YY, Hammer RE, Miyazaki J, Williams SC, Richardson JA, Yanagisawa M. Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev Biol 2001; 230:230-42; PMID:11161575; http://dx.doi.org/10.1006/dbio.2000.0106
   PubMed Web of Science ®Google Scholar