2,126
Views
103
CrossRef citations to date
0
Altmetric
Report

Epithelial-to-mesenchymal transition (EMT) confers primary resistance to trastuzumab (Herceptin)

, , , , , , , & show all
Pages 4020-4032 | Published online: 19 Sep 2012

References

  • Korkaya H, Paulson A, Iovino F, Wicha MS. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 2008; 27:6120 - 30; http://dx.doi.org/10.1038/onc.2008.207; PMID: 18591932
  • Kakarala M, Wicha MS. Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 2008; 26:2813 - 20; http://dx.doi.org/10.1200/JCO.2008.16.3931; PMID: 18539959
  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003; 100:3983 - 8; http://dx.doi.org/10.1073/pnas.0530291100; PMID: 12629218
  • Jones RJ, Matsui WH, Smith BD. Cancer stem cells: are we missing the target?. J Natl Cancer Inst 2004; 96:583 - 5; http://dx.doi.org/10.1093/jnci/djh095; PMID: 15100335
  • Fillmore CM, Kuperwasser C. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res 2008; 10:R25; http://dx.doi.org/10.1186/bcr1982; PMID: 18366788
  • Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 2008; 100:672 - 9; http://dx.doi.org/10.1093/jnci/djn123; PMID: 18445819
  • Debeb BG, Xu W, Woodward WA. Radiation resistance of breast cancer stem cells: understanding the clinical framework. J Mammary Gland Biol Neoplasia 2009; 14:11 - 7; http://dx.doi.org/10.1007/s10911-009-9114-z; PMID: 19252973
  • Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 2008; 26:2839 - 45; http://dx.doi.org/10.1200/JCO.2007.15.1829; PMID: 18539962
  • Nguyen NP, Almeida FS, Chi A, Nguyen LM, Cohen D, Karlsson U, et al. Molecular biology of breast cancer stem cells: potential clinical applications. Cancer Treat Rev 2010; 36:485 - 91; http://dx.doi.org/10.1016/j.ctrv.2010.02.016; PMID: 20231058
  • Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 2007; 356:217 - 26; http://dx.doi.org/10.1056/NEJMoa063994; PMID: 17229949
  • Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA 2009; 106:13820 - 5; http://dx.doi.org/10.1073/pnas.0905718106; PMID: 19666588
  • Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, Cufí S, Del Barco S, Lopez-Bonet E, et al. Dynamic emergence of the mesenchymal CD44(pos)CD24(neg/low) phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin). Biochem Biophys Res Commun 2010; 397:27 - 33; http://dx.doi.org/10.1016/j.bbrc.2010.05.041; PMID: 20470755
  • Vazquez-Martin A, Oliveras-Ferraros C, Del Barco S, Martin-Castillo B, Menendez JA. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat 2011; 126:355 - 64; http://dx.doi.org/10.1007/s10549-010-0924-x; PMID: 20458531
  • Jiang J, Zhang Y, Chuai S, Wang Z, Zheng D, Xu F, et al. Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype. Oncogene 2012; 31:671 - 82; http://dx.doi.org/10.1038/onc.2011.282; PMID: 21743497
  • Liu JC, Voisin V, Bader GD, Deng T, Pusztai L, Symmans WF, et al. Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα- breast cancer. Proc Natl Acad Sci USA 2012; 109:5832 - 7; http://dx.doi.org/10.1073/pnas.1201105109; PMID: 22460789
  • Magnifico A, Albano L, Campaner S, Delia D, Castiglioni F, Gasparini P, et al. Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab. Clin Cancer Res 2009; 15:2010 - 21; http://dx.doi.org/10.1158/1078-0432.CCR-08-1327; PMID: 19276287
  • Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 2008; 358:1409 - 11; http://dx.doi.org/10.1056/NEJMc0801440; PMID: 18367751
  • Liu S, Wicha MS. Targeting breast cancer stem cells. J Clin Oncol 2010; 28:4006 - 12; http://dx.doi.org/10.1200/JCO.2009.27.5388; PMID: 20498387
  • Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20:719 - 26; http://dx.doi.org/10.1200/JCO.20.3.719; PMID: 11821453
  • Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol 2006; 3:269 - 80; http://dx.doi.org/10.1038/ncponc0509; PMID: 16683005
  • Nahta R, Esteva FJ. HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res 2006; 8:215; http://dx.doi.org/10.1186/bcr1612; PMID: 17096862
  • Valabrega G, Montemurro F, Aglietta M. Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol 2007; 18:977 - 84; http://dx.doi.org/10.1093/annonc/mdl475; PMID: 17229773
  • Nahta R, Esteva FJ. Trastuzumab: triumphs and tribulations. Oncogene 2007; 26:3637 - 43; http://dx.doi.org/10.1038/sj.onc.1210379; PMID: 17530017
  • Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 2009; 27:5838 - 47; http://dx.doi.org/10.1200/JCO.2009.22.1507; PMID: 19884552
  • Esteva FJ, Yu D, Hung MC, Hortobagyi GN. Molecular predictors of response to trastuzumab and lapatinib in breast cancer. Nat Rev Clin Oncol 2010; 7:98 - 107; http://dx.doi.org/10.1038/nrclinonc.2009.216; PMID: 20027191
  • Pályi-Krekk Z, Barok M, Isola J, Tammi M, Szöllosi J, Nagy P. Hyaluronan-induced masking of ErbB2 and CD44-enhanced trastuzumab internalisation in trastuzumab resistant breast cancer. Eur J Cancer 2007; 43:2423 - 33; http://dx.doi.org/10.1016/j.ejca.2007.08.018; PMID: 17911008
  • Pályi-Krekk Z, Barok M, Kovács T, Saya H, Nagano O, Szöllosi J, et al. EGFR and ErbB2 are functionally coupled to CD44 and regulate shedding, internalization and motogenic effect of CD44. Cancer Lett 2008; 263:231 - 42; http://dx.doi.org/10.1016/j.canlet.2008.01.014; PMID: 18276068
  • Dawood S, Gong Y, Broglio K, Buchholz TA, Woodward W, Lucci A, et al. Trastuzumab in Primary Inflammatory Breast Cancer (IBC): High Pathological Response Rates and Improved Outcome. Breast J 2010; PMID: 20626396
  • Bao W, Fu HJ, Xie QS, Wang L, Zhang R, Guo ZY, et al. HER2 interacts with CD44 to up-regulate CXCR4 via epigenetic silencing of microRNA-139 in gastric cancer cells. Gastroenterology 2011; 141:2076 - 87, e6; PMID: 21925125
  • Lesniak D, Xu Y, Deschenes J, Lai R, Thoms J, Murray D, et al. Beta1-integrin circumvents the antiproliferative effects of trastuzumab in human epidermal growth factor receptor-2-positive breast cancer. Cancer Res 2009; 69:8620 - 8; http://dx.doi.org/10.1158/0008-5472.CAN-09-1591; PMID: 19887601
  • Osipo C, Patel P, Rizzo P, Clementz AG, Hao L, Golde TE, et al. ErbB-2 inhibition activates Notch-1 and sensitizes breast cancer cells to a gamma-secretase inhibitor. Oncogene 2008; 27:5019 - 32; http://dx.doi.org/10.1038/onc.2008.149; PMID: 18469855
  • Pandya K, Meeke K, Clementz AG, Rogowski A, Roberts J, Miele L, et al. Targeting both Notch and ErbB-2 signalling pathways is required for prevention of ErbB-2-positive breast tumour recurrence. Br J Cancer 2011; 105:796 - 806; http://dx.doi.org/10.1038/bjc.2011.321; PMID: 21847123
  • Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Torres-Garcia VZ, Sauri-Nadal T, Barco SD, et al. Inhibitor of Apoptosis (IAP) survivin is indispensable for survival of HER2 gene-amplified breast cancer cells with primary resistance to HER1/2-targeted therapies. Biochem Biophys Res Commun 2011; 407:412 - 9; http://dx.doi.org/10.1016/j.bbrc.2011.03.039; PMID: 21402055
  • Bedard PL, Cardoso F, Piccart-Gebhart MJ. Stemming resistance to HER-2 targeted therapy. J Mammary Gland Biol Neoplasia 2009; 14:55 - 66; http://dx.doi.org/10.1007/s10911-009-9116-x; PMID: 19259796
  • Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castilló B, Pérez-Martínez MC, Cufí S, Del Barco S, et al. Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin). Int J Oncol 2010; 37:669 - 78; PMID: 20664936
  • Cufi S, Corominas-Faja B, Vazquez-Martin A, Oliveras-Ferraros C, Dorca J, Bosch-Barrera J, et al. Metformin-induced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts. Oncotarget 2012; 3:395 - 8; PMID: 22565037
  • Blick T, Widodo E, Hugo H, Waltham M, Lenburg ME, Neve RM, et al. Epithelial mesenchymal transition traits in human breast cancer cell lines. Clin Exp Metastasis 2008; 25:629 - 42; http://dx.doi.org/10.1007/s10585-008-9170-6; PMID: 18461285
  • Blick T, Hugo H, Widodo E, Waltham M, Pinto C, Mani SA, et al. Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44(hi/)CD24 (lo/-) stem cell phenotype in human breast cancer. J Mammary Gland Biol Neoplasia 2010; 15:235 - 52; http://dx.doi.org/10.1007/s10911-010-9175-z; PMID: 20521089
  • Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006; 10:515 - 27; http://dx.doi.org/10.1016/j.ccr.2006.10.008; PMID: 17157791
  • Tanner M, Kapanen AI, Junttila T, Raheem O, Grenman S, Elo J, et al. Characterization of a novel cell line established from a patient with Herceptin-resistant breast cancer. Mol Cancer Ther 2004; 3:1585 - 92; PMID: 15634652
  • Nagy P, Friedländer E, Tanner M, Kapanen AI, Carraway KL, Isola J, et al. Decreased accessibility and lack of activation of ErbB2 in JIMT-1, a herceptin-resistant, MUC4-expressing breast cancer cell line. Cancer Res 2005; 65:473 - 82; PMID: 15695389
  • Jönsson G, Staaf J, Olsson E, Heidenblad M, Vallon-Christersson J, Osoegawa K, et al. High-resolution genomic profiles of breast cancer cell lines assessed by tiling BAC array comparative genomic hybridization. Genes Chromosomes Cancer 2007; 46:543 - 58; http://dx.doi.org/10.1002/gcc.20438; PMID: 17334996
  • Casas E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ, Yang J. Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res 2011; 71:245 - 54; http://dx.doi.org/10.1158/0008-5472.CAN-10-2330; PMID: 21199805
  • Vesuna F, Lisok A, Kimble B, Raman V. Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression. Neoplasia 2009; 11:1318 - 28; PMID: 20019840
  • Bhat-Nakshatri P, Appaiah H, Ballas C, Pick-Franke P, Goulet R Jr., Badve S, et al. SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24- phenotype. BMC Cancer 2010; 10:411; http://dx.doi.org/10.1186/1471-2407-10-411; PMID: 20691079
  • Meyer MJ, Fleming JM, Ali MA, Pesesky MW, Ginsburg E, Vonderhaar BK. Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines. Breast Cancer Res 2009; 11:R82; http://dx.doi.org/10.1186/bcr2449; PMID: 19906290
  • Kaipparettu BA, Malik S, Konduri SD, Liu W, Rokavec M, van der Kuip H, et al. Estrogen-mediated downregulation of CD24 in breast cancer cells. Int J Cancer 2008; 123:66 - 72; http://dx.doi.org/10.1002/ijc.23480; PMID: 18404683
  • Hajra KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res 2002; 62:1613 - 8; PMID: 11912130
  • Bolós V, Peinado H, Pérez-Moreno MA, Fraga MF, Esteller M, Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci 2003; 116:499 - 511; http://dx.doi.org/10.1242/jcs.00224; PMID: 12508111
  • Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, et al. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 2005; 65:5506 - 11; http://dx.doi.org/10.1158/0008-5472.CAN-05-0626; PMID: 15994920
  • Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS. Stem cells in normal breast development and breast cancer. Cell Prolif 2003; 36:Suppl 1 59 - 72; http://dx.doi.org/10.1046/j.1365-2184.36.s.1.6.x; PMID: 14521516
  • Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res 2010; 70:709 - 18; http://dx.doi.org/10.1158/0008-5472.CAN-09-1681; PMID: 20068161
  • Shaw FL, Harrison H, Spence K, Ablett MP, Simões BM, Farnie G, et al. A detailed mammosphere assay protocol for the quantification of breast stem cell activity. J Mammary Gland Biol Neoplasia 2012; 17:111 - 7; http://dx.doi.org/10.1007/s10911-012-9255-3; PMID: 22665270
  • Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008; 133:704 - 15; http://dx.doi.org/10.1016/j.cell.2008.03.027; PMID: 18485877
  • Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 2008; 3:e2888; http://dx.doi.org/10.1371/journal.pone.0002888; PMID: 18682804
  • Floor S, van Staveren WC, Larsimont D, Dumont JE, Maenhaut C. Cancer cells in epithelial-to-mesenchymal transition and tumor-propagating-cancer stem cells: distinct, overlapping or same populations. Oncogene 2011; 30:4609 - 21; http://dx.doi.org/10.1038/onc.2011.184; PMID: 21643013
  • Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 2010; 9:3807 - 14; http://dx.doi.org/10.4161/cc.9.18.13131; PMID: 20890129
  • Alves CC, Carneiro F, Hoefler H, Becker KF. Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. Front Biosci 2009; 14:3035 - 50; http://dx.doi.org/10.2741/3433; PMID: 19273255
  • Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia 2010; 15:117 - 34; http://dx.doi.org/10.1007/s10911-010-9178-9; PMID: 20490631
  • Hugo HJ, Kokkinos MI, Blick T, Ackland ML, Thompson EW, Newgreen DF. Defining the E-cadherin repressor interactome in epithelial-mesenchymal transition: the PMC42 model as a case study. Cells Tissues Organs 2011; 193:23 - 40; http://dx.doi.org/10.1159/000320174; PMID: 21051859
  • Foubert E, De Craene B, Berx G. Key signalling nodes in mammary gland development and cancer. The Snail1-Twist1 conspiracy in malignant breast cancer progression. Breast Cancer Res 2010; 12:206; http://dx.doi.org/10.1186/bcr2585; PMID: 20594364
  • Kang Y, Massagué J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 2004; 118:277 - 9; http://dx.doi.org/10.1016/j.cell.2004.07.011; PMID: 15294153
  • Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, et al. Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J Cell Physiol 2007; 213:374 - 83; http://dx.doi.org/10.1002/jcp.21223; PMID: 17680632
  • Storci G, Sansone P, Trere D, Tavolari S, Taffurelli M, Ceccarelli C, et al. The basal-like breast carcinoma phenotype is regulated by SLUG gene expression. J Pathol 2008; 214:25 - 37; http://dx.doi.org/10.1002/path.2254; PMID: 17973239
  • Stingl J, Caldas C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat Rev Cancer 2007; 7:791 - 9; http://dx.doi.org/10.1038/nrc2212; PMID: 17851544
  • Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell 2007; 11:259 - 73; http://dx.doi.org/10.1016/j.ccr.2007.01.013; PMID: 17349583
  • Liao MJ, Zhang CC, Zhou B, Zimonjic DB, Mani SA, Kaba M, et al. Enrichment of a population of mammary gland cells that form mammospheres and have in vivo repopulating activity. Cancer Res 2007; 67:8131 - 8; http://dx.doi.org/10.1158/0008-5472.CAN-06-4493; PMID: 17804725
  • Sarrió D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J. Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res 2008; 68:989 - 97; http://dx.doi.org/10.1158/0008-5472.CAN-07-2017; PMID: 18281472
  • Gasparotto D, Polesel J, Marzotto A, Colladel R, Piccinin S, Modena P, et al. Overexpression of TWIST2 correlates with poor prognosis in head and neck squamous cell carcinomas. Oncotarget 2011; 2:1165 - 75; PMID: 22201613
  • Moody SE, Perez D, Pan TC, Sarkisian CJ, Portocarrero CP, Sterner CJ, et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell 2005; 8:197 - 209; http://dx.doi.org/10.1016/j.ccr.2005.07.009; PMID: 16169465
  • Celià-Terrassa T, Meca-Cortés O, Mateo F, de Paz AM, Rubio N, Arnal-Estapé A, et al. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Invest 2012; 122:1849 - 68; http://dx.doi.org/10.1172/JCI59218; PMID: 22505459
  • Li R, Liang J, Ni S, Zhou T, Qing X, Li H, et al. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell 2010; 7:51 - 63; http://dx.doi.org/10.1016/j.stem.2010.04.014; PMID: 20621050
  • Polo JM, Hochedlinger K. When fibroblasts MET iPSCs. Cell Stem Cell 2010; 7:5 - 6; http://dx.doi.org/10.1016/j.stem.2010.05.018; PMID: 20621040
  • Samavarchi-Tehrani P, Golipour A, David L, Sung HK, Beyer TA, Datti A, et al. Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 2010; 7:64 - 77; http://dx.doi.org/10.1016/j.stem.2010.04.015; PMID: 20621051
  • Lowry WE. E-cadherin, a new mixer in the Yamanaka cocktail. EMBO Rep 2011; 12:613 - 4; http://dx.doi.org/10.1038/embor.2011.117; PMID: 21701504
  • Redmer T, Diecke S, Grigoryan T, Quiroga-Negreira A, Birchmeier W, Besser D. E-cadherin is crucial for embryonic stem cell pluripotency and can replace OCT4 during somatic cell reprogramming. EMBO Rep 2011; 12:720 - 6; http://dx.doi.org/10.1038/embor.2011.88; PMID: 21617704
  • Salem AF, Bonuccelli G, Bevilacqua G, Arafat H, Pestell RG, Sotgia F, et al. Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition. Cell Cycle 2011; 10:3692 - 700; http://dx.doi.org/10.4161/cc.10.21.17895; PMID: 22041584
  • Tuma RS. Cancer stem cell hypothesis and trastuzumab in HER2-negative tumors. J Natl Cancer Inst 2012; 104:968 - 9; http://dx.doi.org/10.1093/jnci/djs307; PMID: 22745473
  • Liu B, Fan Z, Edgerton SM, Yang X, Lind SE, Thor AD. Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions. Cell Cycle 2011; 10:2959 - 66; http://dx.doi.org/10.4161/cc.10.17.16359; PMID: 21862872
  • Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010; 29:4741 - 51; http://dx.doi.org/10.1038/onc.2010.215; PMID: 20531305
  • Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Del Barco S, Martin-Castillo B, Menendez JA. Metformin regulates breast cancer stem cell ontogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle 2010; 9:3807 - 14; http://dx.doi.org/10.4161/cc.9.18.13131; PMID: 20890129
  • Wang Z, Li Y, Ahmad A, Azmi AS, Kong D, Banerjee S, et al. Targeting miRNAs involved in cancer stem cell and EMT regulation: An emerging concept in overcoming drug resistance. Drug Resist Updat 2010; 13:109 - 18; http://dx.doi.org/10.1016/j.drup.2010.07.001; PMID: 20692200
  • Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo B, Joven J, Menendez JA. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle 2010; 9:4461 - 8; http://dx.doi.org/10.4161/cc.9.22.14048; PMID: 21088486
  • Takebe N, Warren RQ, Ivy SP. Breast cancer growth and metastasis: interplay between cancer stem cells, embryonic signaling pathways and epithelial-to-mesenchymal transition. Breast Cancer Res 2011; 13:211; http://dx.doi.org/10.1186/bcr2876; PMID: 21672282
  • Del Barco S, Vazquez-Martin A, Cufí S, Oliveras-Ferraros C, Bosch-Barrera J, Joven J, et al. Metformin: multi-faceted protection against cancer. Oncotarget 2011; 2:896 - 917; PMID: 22203527
  • Rattan R, Ali Fehmi R, Munkarah A. Metformin: an emerging new therapeutic option for targeting cancer stem cells and metastasis. J Oncol 2012; 2012:928127; PMID: 22701483
  • Barrière G, Tartary M, Rigaud M. Metformin: A Rising Star to Fight The Epithelial Mesenchymal Transition in Oncology. Anticancer Agents Med Chem 2012; In press

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.