611
Views
80
CrossRef citations to date
0
Altmetric
Reviews

Targeting focal adhesion kinase signaling in tumor growth and metastasis

, &
Pages 77-94 | Published online: 09 Dec 2009

Bibliography

  • Kanner SB, Reynolds AB, Vines RR, Parsons JT. Monoclonal antibodies to individual tyrosine-phosphorylated protein substrates of oncogene-encoded tyrosine kinases. Proc Natl Acad Sci USA 1990;87(9):3328-32
  • Schaller MD, Borgman CA, Cobb BS, pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc Natl Acad Sci USA 1992;89(11):5192-6
  • Hanks SK, Calalb MB, Harper MC, Patel SK. Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc Natl Acad Sci USA 1992;89(18):8487-91
  • Guan JL, Shalloway D. Regulation of focal adhesion-associated protein tyrosine kinase by both cellular adhesion and oncogenic transformation. Nature 1992;358(6388):690-2
  • Schaller MD. Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim Biophys Acta 2001;1540(1):1-21
  • Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 2005;6(1):56-68
  • McLean GW, Carragher NO, Avizienyte E, The role of focal-adhesion kinase in cancer – a new therapeutic opportunity. Nat Rev Cancer 2005;5(7):505-15
  • Ilic D, Furuta Y, Kanazawa S, Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 1995;377(6549):539-44
  • Howerton K, Schlaepfer DD, Ilic D. Establishment of cell lines from mouse embryos with early embryonic lethality. Cell Commun Adhes 2008;15(4):379-83
  • Golubovskaya VM, Finch R, Cance WG. Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53. J Biol Chem 2005;280(26):25008-21
  • Lim ST, Chen XL, Lim Y, Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation. Mol Cell 2008;29(1):9-22
  • Cance WG, Golubovskaya VM. Focal adhesion kinase versus p53: apoptosis or survival? Sci Signal 2008;1(20):pe22. Published online 20 May 2008, doi: 10.1126/stke.120pe22
  • Sieg DJ, Hauck CR, Schlaepfer DD. Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J Cell Sci 1999;112 (Pt 16):2677-91
  • Sieg DJ, Hauck CR, Ilic D, FAK integrates growth-factor and integrin signals to promote cell migration. Nat Cell Biol 2000;2(5):249-56
  • Theocharis SE, Kouraklis GP, Kakisis JD, Focal adhesion kinase expression is not a prognostic predictor in colon adenocarcinoma patients. Eur J Surg Oncol 2003;29(7):571-4
  • Furuyama K, Doi R, Mori T, Clinical significance of focal adhesion kinase in resectable pancreatic cancer. World J Surg 2006;30(2):219-26
  • Gabriel B, zur Hausen A, Stickeler E, Weak expression of focal adhesion kinase (pp125FAK) in patients with cervical cancer is associated with poor disease outcome. Clin Cancer Res 2006;12(8):2476-83
  • Zhao J, Guan JL. Signal transduction by focal adhesion kinase in cancer. Cancer Metastasis Rev 2009;28(1-2):35-49
  • Golubovskaya VM, Kweh FA, Cance WG. Focal adhesion kinase and cancer. Histol Histopathol 2009;24(4):503-10
  • Angelucci A, Bologna M. Targeting vascular cell migration as a strategy for blocking angiogenesis: the central role of focal adhesion protein tyrosine kinase family. Curr Pharm Des 2007;13(21):2129-45
  • Dunty JM, Gabarra-Niecko V, King ML, FERM domain interaction promotes FAK signaling. Mol Cell Biol 2004;24(12):5353-68
  • Chen HC, Guan JL. Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase. Proc Natl Acad Sci USA 1994;91(21):10148-52
  • Zhang X, Chattopadhyay A, Ji QS, Focal adhesion kinase promotes phospholipase C-gamma1 activity. Proc Natl Acad Sci USA 1999;96(16):9021-6
  • Ma A, Richardson A, Schaefer EM, Parsons JT. Serine phosphorylation of focal adhesion kinase in interphase and mitosis: a possible role in modulating binding to p130Cas. Mol Biol Cell 2001;12(1):1-12
  • Jacamo R, Jiang X, Lunn JA, Rozengurt E. FAK phosphorylation at Ser-843 inhibits Tyr-397 phosphorylation, cell spreading and migration. J Cell Physiol 2007;210(2):436-44
  • Dourdin N, Bhatt AK, Dutt P, Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts. J Biol Chem 2001;276(51):48382-8
  • Kadare G, Toutant M, Formstecher E, PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation. J Biol Chem 2003;278(48):47434-40
  • Abbi S, Ueda H, Zheng C, Regulation of focal adhesion kinase by a novel protein inhibitor FIP200. Mol Biol Cell 2002;13(9):3178-91
  • Zeng L, Si X, Yu WP, PTPalpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. J Cell Biol 2003;160(1):137-46
  • Schaller MD, Borgman CA, Parsons JT. Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. Mol Cell Biol 1993;13(2):785-91
  • Bellis SL, Miller JT, Turner CE. Characterization of tyrosine phosphorylation of paxillin in vitro by focal adhesion kinase. J Biol Chem 1995;270(29):17437-41
  • Harte MT, Hildebrand JD, Burnham MR, p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase. J Biol Chem 1996;271(23):13649-55
  • Pylayeva Y, Gillen KM, Gerald W, Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J Clin Invest 2009;119(2):252-66
  • Cho SY, Klemke RL. Purification of pseudopodia from polarized cells reveals redistribution and activation of Rac through assembly of a CAS/Crk scaffold. J Cell Biol 2002;156(4):725-36
  • Ren XD, Kiosses WB, Sieg DJ, Focal adhesion kinase suppresses Rho activity to promote focal adhesion turnover. J Cell Sci 2000;113(Pt 20):3673-8
  • Pirone DM, Liu WF, Ruiz SA, An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling. J Cell Biol 2006;174(2):277-88
  • Le Boeuf F, Houle F, Sussman M, Huot J. Phosphorylation of focal adhesion kinase (FAK) on Ser732 is induced by Rho-dependent kinase and is essential for proline-rich tyrosine kinase-2-mediated phosphorylation of FAK on Tyr407 in response to vascular endothelial growth factor. Mol Biol Cell 2006;17(8):3508-20
  • Turner CE, Brown MC, Perrotta JA, Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: a role in cytoskeletal remodeling. J Cell Biol 1999;145(4):851-63
  • van Miltenburg MH, Lalai R, de Bont H, Complete focal adhesion kinase deficiency in the mammary gland causes ductal dilation and aberrant branching morphogenesis through defects in Rho kinase-dependent cell contractility. FASEB J 2009;23(10):3482-93
  • Shen TL, Park AY, Alcaraz A, Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol 2005;169(6):941-52
  • Braren R, Hu H, Kim YH, Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation. J Cell Biol 2006;172(1):151-62
  • Hakim ZS, DiMichele LA, Doherty JT, Conditional deletion of focal adhesion kinase leads to defects in ventricular septation and outflow tract alignment. Mol Cell Biol 2007;27(15):5352-64
  • Peng X, Wu X, Druso JE, Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice. Proc Natl Acad Sci USA 2008;105(18):6638-43
  • Hay ED. Role of cell-matrix contacts in cell migration and epithelial–mesenchymal transformation. Cell Differ Dev 1990;32(3):367-75
  • Thiery JP, Sleeman JP. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7(2):131-42
  • Wolf K, Friedl P. Molecular mechanisms of cancer cell invasion and plasticity. Br J Dermatol 2006; 154:(Suppl 1):11-5
  • Revenu C, Gilmour D. EMT 2.0: shaping epithelia through collective migration. Curr Opin Genet Dev 2009;19(4):338-42
  • McLean GW, Komiyama NH, Serrels B, Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression. Genes Dev 2004;18(24):2998-3003
  • Weiner TM, Liu ET, Craven RJ, Cance WG. Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors. Ann Surg Oncol 1994;1(1):18-27
  • Owens LV, Xu L, Craven RJ, Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res 1995;55(13):2752-5
  • Chatzizacharias NA, Kouraklis GP, Theocharis SE. Clinical significance of FAK expression in human neoplasia. Histol Histopathol 2008;23(5):629-50
  • Canel M, Secades P, Rodrigo JP, Overexpression of focal adhesion kinase in head and neck squamous cell carcinoma is independent of fak gene copy number. Clin Cancer Res 2006;12(11 Pt 1):3272-9
  • Schwock J, Dhani N, Cao MP, Targeting focal adhesion kinase with dominant-negative FRNK or Hsp90 inhibitor 17-DMAG suppresses tumor growth and metastasis of SiHa cervical xenografts. Cancer Res 2009;69(11):4750-9
  • Ayaki M, Komatsu K, Mukai M, Reduced expression of focal adhesion kinase in liver metastases compared with matched primary human colorectal adenocarcinomas. Clin Cancer Res 2001;7(10):3106-12
  • Hauck CR, Hsia DA, Puente XS, FRNK blocks v-Src-stimulated invasion and experimental metastases without effects on cell motility or growth. EMBO J 2002;21(23):6289-302
  • Sonoda Y, Matsumoto Y, Funakoshi M, Anti-apoptotic role of focal adhesion kinase (FAK). Induction of inhibitor-of-apoptosis proteins and apoptosis suppression by the overexpression of FAK in a human leukemic cell line, HL-60. J Biol Chem 2000;275(21):16309-15
  • Frisch SM, Vuori K, Ruoslahti E, Chan-Hui PY. Control of adhesion-dependent cell survival by focal adhesion kinase. J Cell Biol 1996;134(3):793-9
  • Mitra SK, Mikolon D, Molina JE, Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors. Oncogene 2006;25(44):5969-84
  • Hess AR, Postovit LM, Margaryan NV, Focal adhesion kinase promotes the aggressive melanoma phenotype. Cancer Res 2005;65(21):9851-60
  • Skuli N, Monferran S, Delmas C, alphavbeta3/alphavbeta5 integrins-FAK-RhoB: a novel pathway for hypoxia regulation in glioblastoma. Cancer Res 2009;69(8):3308-16
  • Lahlou H, Sanguin-Gendreau V, Zuo D, Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression. Proc Natl Acad Sci USA 2007;104(51):20302-7
  • Provenzano PP, Inman DR, Eliceiri KW, Mammary epithelial-specific disruption of focal adhesion kinase retards tumor formation and metastasis in a transgenic mouse model of human breast cancer. Am J Pathol 2008;173(5):1551-65
  • Golubovskaya V, Kaur A, Cance W. Cloning and characterization of the promoter region of human focal adhesion kinase gene: nuclear factor kappa B and p53 binding sites. Biochim Biophys Acta 2004;1678(2-3):111-25
  • Beierle EA, Trujillo A, Nagaram A, N-MYC regulates focal adhesion kinase expression in human neuroblastoma. J Biol Chem 2007;282(17):12503-16
  • Lim ST, Mikolon D, Stupack DG, Schlaepfer DD. FERM control of FAK function: implications for cancer therapy. Cell Cycle 2008;7(15):2306-14
  • Kurenova E, Xu LH, Yang X, Focal adhesion kinase suppresses apoptosis by binding to the death domain of receptor-interacting protein. Mol Cell Biol 2004;24(10):4361-71
  • van Nimwegen MJ, Verkoeijen S, van Buren L, Requirement for focal adhesion kinase in the early phase of mammary adenocarcinoma lung metastasis formation. Cancer Res 2005;65(11):4698-706
  • Shibata K, Kikkawa F, Nawa A, Both focal adhesion kinase and c-Ras are required for the enhanced matrix metalloproteinase 9 secretion by fibronectin in ovarian cancer cells. Cancer Res 1998 58(5):900-3
  • Mitra SK, Lim ST, Chi A, Schlaepfer DD. Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model. Oncogene 2006;25(32):4429-40
  • Avizienyte E, Frame MC. Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition. Curr Opin Cell Biol 2005;17(5):542-7
  • Avizienyte E, Wyke AW, Jones RJ, Src-induced de-regulation of E-cadherin in colon cancer cells requires integrin signalling. Nat Cell Biol 2002;4(8):632-8
  • Cicchini C, Laudadio I, Citarella F, TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling. Exp Cell Res 2008;314(1):143-52
  • Bailey KM, Liu J. Caveolin-1 up-regulation during epithelial to mesenchymal transition is mediated by focal adhesion kinase. J Biol Chem 2008;283(20):13714-24
  • Tilghman RW, Parsons JT. Focal adhesion kinase as a regulator of cell tension in the progression of cancer. Semin Cancer Biol 2008;18(1):45-52
  • Carragher NO, Walker SM, Scott Carragher LA, Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function. Oncogene 2006;25(42):5726-40
  • Sanz-Moreno V, Gadea G, Ahn J, Rac activation and inactivation control plasticity of tumor cell movement. Cell 2008;135(3):510-23
  • Parri M, Taddei ML, Bianchini F, EphA2 reexpression prompts invasion of melanoma cells shifting from mesenchymal to amoeboid-like motility style. Cancer Res 2009;69(5):2072-81
  • Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002;295(5564):2387-92
  • Kasaoka T, Nishiyama H, Okada M, Nakajima M. Matrix metalloproteinase inhibitor, MMI270 (CGS27023A) inhibited hematogenic metastasis of B16 melanoma cells in both experimental and spontaneous metastasis models. Clin Exp Metastasis 2008;25(7):827-34
  • Mani SA, Guo W, Liao MJ, The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 2008;133(4):704-15
  • Luo M, Fan H, Nagy T, Mammary epithelial-specific ablation of the focal adhesion kinase suppresses mammary tumorigenesis by affecting mammary cancer stem/progenitor cells. Cancer Res 2009;69(2):466-74
  • Luo M, Guan JL. Focal adhesion kinase: a prominent determinant in breast cancer initiation, progression and metastasis. Cancer Lett 2009: published online 29 July 2009 doi:10.1016/j.canlet.2009.07.005
  • Xu LH, Owens LV, Sturge GC, Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells. Cell Growth Differ 1996;7(4):413-8
  • Xu LH, Yang X, Craven RJ, Cance WG. The COOH-terminal domain of the focal adhesion kinase induces loss of adhesion and cell death in human tumor cells. Cell Growth Differ 1998;9(12):999-1005
  • Slack-Davis JK, Martin KH, Tilghman RW, Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem 2007;282(20):14845-52
  • Lietha D, Eck MJ. Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation. PLoS ONE 2008;3(11):e3800. Published online 24 November 2008, doi:10.1371/journal.pone.0003800
  • Roberts WG, Ung E, Whalen P, Antitumor activity and pharmacology of a selective focal adhesion kinase inhibitor, PF-562,271. Cancer Res 2008;68(6):1935-44
  • Weis SM, Lim ST, Lutu-Fuga KM, Compensatory role for Pyk2 during angiogenesis in adult mice lacking endothelial cell FAK. J Cell Biol 2008;181(1):43-50
  • Bagi CM, Roberts GW, Andresen CJ. Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors: implications for bone metastases. Cancer 2008;112(10):2313-21
  • Behmoaram E, Bijian K, Jie S, Focal adhesion kinase-related proline-rich tyrosine kinase 2 and focal adhesion kinase are co-overexpressed in early-stage and invasive ErbB-2-positive breast cancer and cooperate for breast cancer cell tumorigenesis and invasiveness. Am J Pathol 2008;173(5):1540-50
  • Bagi CM, Christensen J, Cohen DP, Sunitinib and PF-562,271 (FAK/Pyk2 inhibitor) effectively block growth and recovery of human hepatocellular carcinoma in a rat xenograft model. Cancer Biol Ther 2009;8(9):856-65
  • Siu LL, Burris HA, Mileshkin LR, A phase I clinical, pharmacokinetic (PK) and pharmacodynamic (PD) evaluation of PF-00562271 targeting focal adhesion kinase (FAK) in patients (pts) with advanced solid tumors. ASCO Annual Meeting Proceedings. J Clin Oncol 2008;26(Suppl): abstract 3534
  • Beierle EA, Trujillo A, Nagaram A, TAE226 inhibits human neuroblastoma cell survival. Cancer Invest 2008;26(2):145-51
  • Golubovskaya VM, Virnig C, Cance WG. TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR. Mol Carcinog 2008;47(3):222-34
  • Halder J, Lin YG, Merritt WM, Therapeutic efficacy of a novel focal adhesion kinase inhibitor TAE226 in ovarian carcinoma. Cancer Res 2007;67(22):10976-83
  • Sakurama K, Noma K, Takaoka M, Inhibition of focal adhesion kinase as a potential therapeutic strategy for imatinib-resistant gastrointestinal stromal tumor. Mol Cancer Ther 2009;8(1):127-34
  • Wang ZG, Fukazawa T, Nishikawa T, TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncol Rep 2008;20(6):1473-7
  • Watanabe N, Takaoka M, Sakurama K, Dual tyrosine kinase inhibitor for focal adhesion kinase and insulin-like growth factor-I receptor exhibits anticancer effect in esophageal adenocarcinoma in vitro and in vivo. Clin Cancer Res 2008;14(14):4631-9
  • Shi Q, Hjelmeland AB, Keir ST, A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits glioma growth. Mol Carcinog 2007;46(6):488-96
  • Halder J, Kamat AA, Landen CN Jr, Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin Cancer Res 2006;12(16):4916-24
  • Tsutsumi S, Beebe K, Neckers L. Impact of heat-shock protein 90 on cancer metastasis. Future Oncol 2009;5(5):679-88
  • Whitesell L, Mimnaugh EG, De Costa B, Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 1994;91(18):8324-8
  • Available from: http://www.picard.ch/downloads/downloads.htm
  • Ochel HJ, Schulte TW, Nguyen P, The benzoquinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase. Mol Genet Metab 1999;66(1):24-30
  • Aoyagi Y, Fujita N, Tsuruo T. Stabilization of integrin-linked kinase by binding to Hsp90. Biochem Biophys Res Commun 2005;331(4):1061-8
  • Eustace BK, Sakurai T, Stewart JK, Functional proteomic screens reveal an essential extracellular role for hsp90alpha in cancer cell invasiveness. Nat Cell Biol 2004;6(6):507-14
  • Yang Y, Rao R, Shen J, Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion. Cancer Res 2008;68(12):4833-42
  • Kamal A, Thao L, Sensintaffar J, A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003;425(6956):407-10
  • Taldone T, Sun W, Chiosis G. Discovery and development of heat shock protein 90 inhibitors. Bioorg Med Chem 2009;17(6):2225-35
  • Zagzag D, Nomura M, Friedlander DR, Geldanamycin inhibits migration of glioma cells in vitro: a potential role for hypoxia-inducible factor (HIF-1alpha) in glioma cell invasion. J Cell Physiol 2003;196(2):394-402
  • Utsubo R, Sonoda Y, Takahashi R, Proteome analysis of focal adhesion kinase (FAK)-overexpressing cells. Biol Pharm Bull 2004;27(11):1735-41
  • Koga F, Tsutsumi S, Neckers LM. Low dose geldanamycin inhibits hepatocyte growth factor and hypoxia-stimulated invasion of cancer cells. Cell Cycle 2007;6(11):1393-402
  • Kim MS, Kwak HJ, Lee JW, 17-Allylamino-17-demethoxygeldanamycin down-regulates hyaluronic acid-induced glioma invasion by blocking matrix metalloproteinase-9 secretion. Mol Cancer Res 2008;6(11):1657-65
  • Lang SA, Klein D, Moser C, Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo. Mol Cancer Ther 2007;6(3):1123-32
  • Moser C, Lang SA, Kainz S, Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo. Mol Cancer Ther 2007;6(11):2868-78
  • Lang SA, Moser C, Gaumann A, Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-I receptor signaling, disrupts an interleukin-6/signal-transducer and activator of transcription 3/hypoxia-inducible factor-1alpha autocrine loop, and reduces orthotopic tumor growth. Clin Cancer Res 2007;13(21):6459-68
  • Lang SA, Moser C, Fichnter-Feigl S, Targeting heat-shock protein 90 improves efficacy of rapamycin in a model of hepatocellular carcinoma in mice. Hepatology 2009;49(2):523-32
  • Amiri A, Noei F, Feroz T, Lee JM. Geldanamycin anisimycins activate Rho and stimulate Rho- and ROCK-dependent actin stress fiber formation. Mol Cancer Res 2007;5(9):933-42
  • Price JT, Quinn JM, Sims NA, The heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line. Cancer Res 2005;65(11):4929-38
  • Yano A, Tsutsumi S, Soga S, Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone. Proc Natl Acad Sci USA 2008;105(40):15541-6
  • Rousseau S, Houle F, Kotanides H, Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase. J Biol Chem 2000;275(14):10661-72
  • Le Boeuf F, Houle F, Huot J. Regulation of vascular endothelial growth factor receptor 2-mediated phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase activities. J Biol Chem 2004;279(37):39175-85
  • Sanderson S, Valenti M, Gowan S, Benzoquinone ansamycin heat shock protein 90 inhibitors modulate multiple functions required for tumor angiogenesis. Mol Cancer Ther 2006;5(3):522-32
  • Tsutsumi S, Neckers L. Extracellular heat shock protein 90: a role for a molecular chaperone in cell motility and cancer metastasis. Cancer Sci 2007;98(10):1536-9
  • Golubovskaya VM, Nyberg C, Zheng M, A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the Y397 site of focal adhesion kinase decreases tumor growth. J Med Chem 2008;51(23):7405-16
  • Hochwald SN, Nyberg C, Zheng M, A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle 2009;8(15):2435-43
  • Smith CS, Golubovskaya VM, Peck E, Effect of focal adhesion kinase (FAK) downregulation with FAK antisense oligonucleotides and 5-fluorouracil on the viability of melanoma cell lines. Melanoma Res 2005;15(5):357-62
  • Yang YC, Ho TC, Chen SL, Inhibition of cell motility by troglitazone in human ovarian carcinoma cell line. BMC Cancer 2007;7:216. Published online 20 November 2007, doi:10.1186/1471-2407-7-216
  • Wang PS, Chou FS, Porchia L, Troglitazone inhibits cell migration, adhesion, and spreading by modulating cytoskeletal rearrangement in human breast cancer cells. Mol Carcinog 2008;47(12):905-15
  • Magenta G, Borenstein X, Rolando R, Jasnis MA. Rosiglitazone inhibits metastasis development of a murine mammary tumor cell line LMM3. BMC Cancer 2008;8:47. Published online 8 February 2008, doi:10.1186/1471-2407-8-47
  • Huang YT, Lee LT, Lee PP, Targeting of focal adhesion kinase by flavonoids and small-interfering RNAs reduces tumor cell migration ability. Anticancer Res 2005;25(3B):2017-25
  • Lee JC, Tsai CY, Kao JY, Geraniin-mediated apoptosis by cleavage of focal adhesion kinase through up-regulation of Fas ligand expression in human melanoma cells. Mol Nutr Food Res 2008;52(6):655-63
  • Xu Y, Benlimame N, Su J, Regulation of focal adhesion turnover by ErbB signalling in invasive breast cancer cells. Br J Cancer 2009;100(4):633-43
  • Wang SE, Xiang B, Zent R, Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton. Cancer Res 2009;69(2):475-82
  • Modi S, Stopeck AT, Gordon MS, Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a Phase I dose-escalation study. J Clin Oncol 2007;25(34):5410-7
  • Kobayashi H, Azumi M, Kimura Y, Focal adhesion kinase as an immunotherapeutic target. Cancer Immunol Immunother 2009;58(6):931-40
  • Yang TH, Chen CT, Wang CP, Lou PJ. Photodynamic therapy suppresses the migration and invasion of head and neck cancer cells in vitro. Oral Oncol 2007;43(4):358-65
  • Chan KT, Cortesio CL, Huttenlocher A. FAK alters invadopodia and focal adhesion composition and dynamics to regulate breast cancer invasion. J Cell Biol 2009;185(2):357-70
  • Sieg DJ, Ilic D, Jones KC, Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to enhance FAK- cell migration. EMBO J 1998;17(20):5933-47
  • Klingbeil CK, Hauck CR, Hsia DA, Targeting Pyk2 to beta1-integrin-containing focal contacts rescues fibronectin-stimulated signaling and haptotactic motility defects of focal adhesion kinase-null cells. J Cell Biol 2001;152(1):97-110
  • Yano H, Mazaki Y, Kurokawa K, Roles played by a subset of integrin signaling molecules in cadherin-based cell-cell adhesion. J Cell Biol 2004;166(2):283-95
  • Lu Z, Jiang G, Blume-Jensen P, Hunter T. Epidermal growth factor-induced tumor cell invasion and metastasis initiated by dephosphorylation and downregulation of focal adhesion kinase. Mol Cell Biol 2001;21(12):4016-31
  • Wolf K, Mazo I, Leung H, Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 2003;160(2):267-77
  • Basson MD. An intracellular signal pathway that regulates cancer cell adhesion in response to extracellular forces. Cancer Res 2008;68(1):2-4
  • Paez-Ribes M, Allen E, Hudock J, Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009;15(3):220-31
  • Ebos JM, Lee CR, Cruz-Munoz W, Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009;15(3):232-9
  • Xiong YQ, Sun HC, Zhang W, Human hepatocellular carcinoma tumor-derived endothelial cells manifest increased angiogenesis capability and drug resistance compared with normal endothelial cells. Clin Cancer Res 2009;15(15):4838-46
  • Li S, Hua ZC. FAK expression regulation and therapeutic potential. Adv Cancer Res 2008;101:45-61
  • Bendell JC, Domchek SM, Burstein HJ, Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 2003;97(12):2972-7
  • Yamaguchi K, Takagi Y, Aoki S, Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg 2000;232(1):58-65
  • Biswas S, Guix M, Rinehart C, Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J Clin Invest 2007;117(5):1305-13
  • Creighton CJ, Li X, Landis M, Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 2009;106(33):13820-5
  • Slack-Davis JK, Hershey ED, Theodorescu D, Differential requirement for focal adhesion kinase signaling in cancer progression in the transgenic adenocarcinoma of mouse prostate model. Mol Cancer Ther 2009;8(8):2470-7
  • Hugo H, Ackland ML, Blick T, Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 2007;213(2):374-83
  • Tlsty TD, Coussens LM. Tumor stroma and regulation of cancer development. Annu Rev Pathol 2006;1:119-50
  • Wendt MK, Schiemann WP. Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-beta signaling and metastasis. Breast Cancer Res 2009;11(5):R68. Published online 9 September 2009, doi:10.1186/bcr2360
  • Liu TJ, LaFortune T, Honda T, Inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor kinase suppresses glioma proliferation in vitro and in vivo. Mol Cancer Ther 2007;6(4):1357-67

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.