Stem cell property epithelial-to-mesenchymal transition is a core transcriptional network for predicting cetuximab (erbituxTM) efficacy in KRAS wild-type tumor cells

Journal of Cellular Biochemistry

Volumn 112, Issue 1, 2011, Pages 10-29

  Oliveras Ferraros, Cristina ^a,b   Vazquez Martin, Alejandro ^a,b   Cufí, Sílvia ^a,b   Queralt, Bernardo ^a,b   Báez, Luciana ^a,b   Guardeño, Raquel ^a,b   Hernández Yagü e, Xavier ^a,b   Martin Castillo, Begoña ^a,b   Brunet, Joan ^a,b   Menendez, Javier A ^a,b  

^a CATALAN INSTITUTE OF ONCOLOGY   (Spain)

^b GIRONA BIOMEDICAL RESEARCH INSTITUTE IDIBGI   (Spain)

Author keywords

Cetuximab; EGFR ligands; EMT; KRAS; Stem cells

Indexed keywords

AMPHIREGULIN; BIOLOGICAL MARKER; CD24 ANTIGEN; CD44V ANTIGEN; CETUXIMAB; DUAL SPECIFICITY PHOSPHATASE 6; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; F ACTIN; GEFITINIB; INTEGRIN; K RAS PROTEIN; KERATIN; LAPATINIB; MITOGEN ACTIVATED PROTEIN KINASE; OCCLUDIN; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA; TRASTUZUMAB; UVOMORULIN;

ACTIN FILAMENT; ARTICLE; CANCER STEM CELL; CELL COMMUNICATION; CELL DIFFERENTIATION; CELL MIGRATION; CELL POPULATION; COLORECTAL CANCER; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOSKELETON; DNA MICROARRAY; DOWN REGULATION; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVATION; EPIDERMOID TUMOR; EPITHELIAL MESENCHYMAL TRANSITION; FLOW CYTOMETRY; FOCAL ADHESION; GENE AMPLIFICATION; GENETIC SCREENING; GENETIC TRANSCRIPTION; GENOME ANALYSIS; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; IMMUNOPHENOTYPING; METASTASIS; NEGATIVE FEEDBACK; NUCLEOTIDE SEQUENCE; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TUMOR CELL; UNINDEXED SEQUENCE; UPREGULATION; WILD TYPE;

ANTIBODIES, MONOCLONAL; ANTIGENS, CD24; ANTIGENS, CD44; ANTINEOPLASTIC AGENTS; CARCINOMA, SQUAMOUS CELL; CELL LINE, TUMOR; DOWN-REGULATION; EPITHELIAL-MESENCHYMAL TRANSITION; FEMALE; GENE REGULATORY NETWORKS; HUMANS; NEOPLASMS, SQUAMOUS CELL; PROTO-ONCOGENE PROTEINS; RAS PROTEINS; RECEPTOR, EPIDERMAL GROWTH FACTOR; VULVAR NEOPLASMS;

GASTROPODA;

EID: 78651318026     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.22952     Document Type: Article

References (77)

1. Aoki KF, Kanehisa M. 2005. Using the KEGG database resource. Curr Protoc Bioinformatics (Chapter 1: Unit 1.12).
2. Arnoletti JP, Frolov A, Eloubeidi M, Keene K, Posey J, Wood T, Greeno E, Jhala N, Varadarajulu S, Russo S, Christein J, Oster R, Buchsbaum DJ, Vickers SM. 2010. A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer. Cancer Chemother Pharmacol [Epub ahead of print].
3. Baker JB, Dutta D, Watson D, Maddala T, Shak S, Rowinsky EK, Xu L, Clark E, Mauro DJ, Khambata-Ford S. 2008. Evaluation of tumor gene expression and K-Ras mutations in FFPE tumor tissue as predictors of response to cetuximab in metastatic colorectal cancer [Abstract]. J Clin Oncol 27(Suppl.): 3512.
4. Bardelli A, Siena S. 2010. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol 28:1254-1261.
5. Bates RC. 2005. Colorectal cancer progression: Integrin alphavbeta6 and the epithelial-mesenchymal transition (EMT). Cell Cycle 4:1350-1352.
6. Bedard PL, Cardoso F, Piccart-Gebhart MJ. 2009. Stemming resistance to HER-2 targeted therapy. J Mammary Gland Biol Neoplasia 14:55-66.
7. Bianchi A, Gervasi ME, Bakin AV. 2010. Role of beta5-integrin in epithelialmesenchymal transition in response to TGFbeta. Cell Cycle 9:1647-1659.
8. Blick T, Hugo H, Widodo E, Waltham M, Pinto C, Mani SA, Weinberg RA, Neve RM, Lenburg ME, Thompson EW. 2010. 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 15:235-252.
9. Booth BW, Boulanger CA, Anderson LH, Jimenez-Rojo L, Brisken C, Smith GH. 2010. Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics. Exp Cell Res 316:422-432.
10. Chng Z, Teo A, Pedersen RA, Vallier L. 2010. SIP1 mediates cell-fate decisions between neuroectoderm and mesendoderm in human pluripotent stem cells. Cell Stem Cell 6:59-70.
11. Cicchini C, Laudadio I, Citarella F, Corazzari M, Steindler C, Conigliaro A, Fantoni A, Amicone L, Tripodi M. 2008. TGFbeta-induced EMT requires focal adhesion kinase (FAK) signaling. Exp Cell Res 314:143-152.
12. Citri A, Yarden Y. 2006. EGF-ERBB signalling: Towards the systems level. Nat Rev Mol Cell Biol 7:505-516.
13. de Reyniès A, Boige V, Milano G, Faivre J, Laurent-Puig P. 2008. KRAS mutation signature in colorectal tumors significantly overlaps with the cetuximab response signature. J Clin Oncol 26:2228-2230 (author reply: 2230-2231).
14. De Roock W, Fieuws S, Biesmans B, Jacobs B, De Schutter Y, Humblet Y, Peeters M, Van Cutsem E, Tejpar S. 2009. DUSP expression as a predictor of outcome after cetuximab treatment in Kras wild type and mutant colorectal tumors. ASCO Gastrointestinal Cancers Symposium. Abstract #289.
15. Ettinger DS. 2010. Emerging profile of cetuximab in non-small cell lung cancer. Lung Cancer 68:332-337.
16. Freytag J, Wilkins-Port CE, Higgins CE, Higgins SP, Samarakoon R, Higgins PJ. 2010. PAI-1 mediates the TGF-beta1+EGF-induced "scatter" response in transformed human keratinocytes. J Invest Dermatol 130:2179-2190.
17. Fuxe J, Vincent T, de Herreros AG. 2010. Transcriptional crosstalk between TGFbeta and stem cell pathways in tumor cell invasion: Role of EMT promoting Smad complexes. Cell Cycle 9:2363-2374.
18. Gattenlöhner S, Etschmann B, Kunzmann V, Thalheimer A, Hack M, Kleber G, Einsele H, Germer C, Müller-Hermelink HK. 2009. Concordance of KRAS/ BRAF mutation status in metastatic colorectal cancer before and after anti- EGFR therapy. J Oncol 2009:831626.
19. Gotzmann J, Fischer AN, Zojer M, Mikula M, Proell V, Huber H, JechlingerM, Waerner T, Weith A, Beug H, Mikulits W. 2006. A crucial function of PDGF in TGF-beta-mediated cancer progression of hepatocytes. Oncogene 25:3170-3185.
20. Hartsock A, Nelson WJ. 2008. Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778:660-669.
21. Hawkes E, Cunningham D. 2010. Relationship between colorectal cancer biomarkers and response to epidermal growth factor receptor monoclonal antibodies. J Clin Oncol 28:e529-e531 (author reply e 532-533).
22. Hynes NE, Lane HA. 2005. ERBB receptors and cancer: The complexity of targeted inhibitors. Nat Rev Cancer 5:341-354.
23. Hynes NE, MacDonald G. 2009. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol 21:177-184.
24. Italiano A, Hostein I, Soubeyran I, Fabas T, Benchimol D, Evrard S, Gugenheim J, Becouarn Y, Brunet R, Fonck M, François E, Saint-Paul MC, Pedeutour F. 2010. KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: Biological and clinical implications. Ann Surg Oncol 17:1429-1434.
25. Jacobs B, De Roock W, Piessevaux H, Van Oirbeek R, Biesmans B, De Schutter J, Fieuws S, Vandesompele J, Peeters M, Van Laethem JL, Humblet Y, Pénault-Llorca F, De Hertogh G, Laurent-Puig P, Van Cutsem E, Tejpar S. 2009. Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab. J Clin Oncol 27:5068-5074.
26. Keise SM. 2008. Dual-specificity MAP kinase phosphatases (MKPs) and cancer. Cancer Metastasis Rev 27:253-261.
27. Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA III, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ. 2007. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25:3230-3237.
28. Korkaya H, Paulson A, Iovino F, Wicha MS. 2008. HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27:6120-6230.
29. Kokkinos MI, Wafai R, Wong MK, Newgreen DF, Thompson EW, Waltham M. 2007. Vimentin and epithelial-mesenchymal transition in human breast cancer - Observations in vitro and in vivo. Cells Tissues Organs 185:191-203.
30. Kurrey NK, Jalgaonkar SP, Joglekar AV, Ghanate AD, Chaskar PD, Doiphode RY, Bapat SA. 2009. Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells 27:2059-2068.
31. Li C, Scott DA, Hatch E, Tian X, Mansour SL. 2007. Dusp6 (Mkp3) is a negative feedback regulator of FGF-stimulated ERK signaling during mouse development. Development 134:167-176.
32. Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC. 2008. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J. Natl Cancer Inst 100:672-679.
33. Linardou H, Dahabreh IJ, Kanaloupiti D, Siannis F, Bafaloukos D, Kosmidis P, Papadimitriou CA, Murray S. 2008. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: A systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9:962-972.
34. Liu S, Wicha MS. 2010. Targeting breast cancer stem cells. J Clin Oncol 28:4006-4012.
35. Lu Y, Li X, Liang K, Luwor R, Siddik ZH, Mills GB, Mendelsohn J, Fan Z. 2007. Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab. Cancer Res 67:8240-8247.
36. Lu Z, Ghosh S, Wang Z, Hunter T. 2003. Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell 4:499-515.
37. Magnifico A, Albano L, Campaner S, Delia D, Castiglioni F, Gasparini P, Sozzi G, Fontanella E, Menard S, Tagliabue E. 2009. Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab. Clin Cancer Res 15:2010-2021.
38. Mandic R, Rodgarkia-Dara CJ, Zhu L, Folz BJ, Bette M, Weihe E, Neubauer A, Werner JÁ 2006. Treatment of HNSCC cell lines with the EGFR-specific inhibitor cetuximab (Erbitux) results in paradox phosphorylation of tyrosine 1173 in the receptor. FEBS Lett 580:4793-4800.
39. Massagué J. 2008. TGFbeta in cancer. Cell 134:215-230.
40. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. 2008. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704-715.
41. Mehra R, Cohen RB, Burtness BA. 2008. The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck. Clin Adv Hematol Oncol 6:742-750.
42. Milsom C, Anderson GM, Weitz JI, Rak J. 2007. Elevated tissue factor procoagulant activity in CD133-positive cancer cells. J Thromb Haemost 5:2550-2552.
43. Milsom CC, Yu JL, Mackman N, Micallef J, Anderson GM, Guha A, Rak JW. 2008. Tissue factor regulation by epidermal growth factor receptor and epithelial-to-mesenchymal transitions: Effect on tumor initiation and angiogenesis. Cancer Res 68:10068-10076.
44. Milsom C, Magnus N, Meehan B, Al-Nedawi K, Garnier D, Rak J. 2009. Tissue factor and cancer stem cells: Is there a linkage? Arterioscler Thromb Vasc Biol 29:2005-2014.
45. Monteiro J, Fodde R. 2010. Cancer stemness and metastasis: Therapeutic consequences and perspectives. Eur J Cancer 46:1198-1203.
46. Morel AP, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A. 2008. Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3:e2888.
47. Moreno-Bueno G, Portillo F, Cano A. 2008. Transcriptional regulation of cell polarity in EMT and cancer. Oncogene 27:6958-6969.
48. Moreno-Bueno G, Peinado H, Molina P, Olmeda D, Cubillo E, Santos V, Palacios J, Portillo F, Cano A. 2009. The morphological and molecular features of the epithelial-to-mesenchymal transition. Nat Protoc 4:1591-1613.
49. Moustakas A, Heldin CH. 2007. Signaling networks guiding epithelialmesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 98:1512-1520.
50. Oliveras-Ferraros C, Vazquez-Martin A, López-Bonet E, Martín-Castillo B, Del Barco S, Brunet J, Menendez JA. 2008. Growth and molecular interactions of the anti-EGFR antibody cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: New prospects in the treatment of triple-negative/basal-like breast cancer. Int J Oncol 33:1165-1176.
51. Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, Cufí S, Del Barco S, Lopez-Bonet E, Brunet J, Menendez JA. 2010a. 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 397:27-33.
52. Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castilló B, Pérez-Martínez MC, Cufí S, Del Barco S, Bernado L, Brunet J, López-Bonet E, Menendez JA. 2010b. 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 37:669-678.
53. Paccione RJ, Miyazaki H, Patel V, Waseem A, Gutkind JS, Zehner ZE, Yeudall WA. 2008. Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility. Mol Cancer Ther 7:2894-2903.
54. Peinado H, Olmeda D, Cano A. 2007. Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype? Nat Rev Cancer 7:415-428.
55. Pueyo G, Mesia R, Figueras A, Lozano A, Baro M, Vazquez S, Capella G, Balart J. 2010. Cetuximab may inhibit tumor growth and angiogenesis induced by ionizing radiation: A preclinical rationale for maintenance treatment after radiotherapy. Oncologist 15:976-986.
56. Reya T, Morrison SJ, Clarke MF, Weissman IL. 2001. Stem cells, cancer, and cancer stem cells. Nature 414:105-111.
57. Rosell R, Morán T, Carcereny E, Quiroga V, Molina MA, Costa C, Benlloch S, Tarón M. 2010. Non-small-cell lung cancer harbouring mutations in the EGFR kinase domain. Clin Transl Oncol 12:75-80.
58. Samarakoon R, Higgins CE, Higgins SP, Higgins PJ. 2009. TGF-beta1- induced expression of the poor prognosis SERPINE1/PAI-1 gene requires EGFR signaling: A new target for anti-EGFR therapy. J Oncol 2009:342391.
59. Sánchez-Muñoz A, Gallego E, de Luque V, Pérez-Rivas LG, Vicioso L, Ribelles N, Lozano J, Alba E. 2010. Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer. BMC Cancer 10:136.
60. Santini D, Spoto C, Loupakis F, Vincenzi B, Silvestris N, Cremolini C, Canestrari E, Graziano F, Galluccio N, Salvatore L, Caraglia M, Zito FA, Colucci G, Falcone A, Tonini G, Ruzzo A. 2010. High concordance of BRAF status between primary colorectal tumours and related metastatic sites: Implications for clinical practice. Ann Oncol 21:1565.
61. Siena S, Sartore-Bianchi A, Di Nicolantonio F, Balfour J, Bardelli A. 2009. Biomarkers predicting clinical outcome of epidermal growth factor receptortargeted therapy in metastatic colorectal cancer. J Natl Cancer Inst 101:1308-1324.
62. Singh A, Settleman J. 2010. EMT, cancer stem cells and drug resistance: An emerging axis of evil in the war of cancer. Oncogene 29:4741-4751.
63. Skvortsova I, Skvortsov S, Raju U, Stasyk T, Riesterer O, Schottdorf EM, Popper BA, Schiestl B, Eichberger P, Debbage P, Neher A, Bonn GK, Huber LA, Milas L, Lukas P. 2010. Epithelial-to-mesenchymal transition and c-myc expression are the determinants of cetuximab-induced enhancement of squamous cell carcinoma radioresponse. Radiother Oncol 96:108-115.
64. Smith G, Bounds R, Wolf H, Steele RJ, Carey FA, Wolf CR. 2010. Activating K-Ras mutations outwith 'hotspot' codons in sporadic colorectal tumours - Implications for personalised cancer medicine. Br J Cancer 102:693-703.
65. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. 2005. Gene set enrichment analysis: A knowledge-based approach for interpreting genomewide expression profiles. Proc Natl Acad Sci USA 102:15545-15550.
66. Thiery JP, Acloque H, Huang RY, Nieto MA. 2009. Epithelial-mesenchymal transitions in development and disease. Cell 139:871-890.
67. Uttamsingh S, Bao X, Nguyen KT, Bhanot M, Gong J, Chan JL, Liu F, Chu TT, Wang LH. 2008. Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells. Oncogene 27:2626-2634.
68. Vazquez-Martin A, Oliveras-Ferraros C, Barco SD, Martin-Castillo B, Menendez JA. 2010. The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells. Breast Cancer Res Treat [Epub ahead of print].
69. Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J, Kerbel RS. 2001. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: A role for altered tumor angiogenesis. Cancer Res 61:5090-5101.
70. Vincent T, Neve EP, Johnson JR, Kukalev A, Rojo F, Albanell J, Pietras K, Virtanen I, Philipson L, Leopold PL, Crystal RG, de Herreros AG, Moustakas A, Pettersson RF, Fuxe J. 2009. A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol 11:943-950.
71. Weber A, Langhanki L, Sommerer F, Markwarth A, Wittekind C, Tannapfel A. 2003. Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 22:4757-4759. (Pubitemid 36976451)
72. Wendt MK, Smith JA, SchiemannWP. 2010. Transforming growth factor-betainduced epithelial-mesenchymal transition facilitates epidermal growth factordependent breast cancer progression. Oncogene [Epub ahead of print].
73. Wharton K, Derynck R. 2009. TGFbeta family signaling: Novel insights in development and disease. Development 136:3691-3697.
74. Wheeler DL, Dunn EF, Harari PM. 2010. Understanding resistance to EGFR inhibitors-impact on future treatment strategies. Nat Rev Clin Oncol 7:493-507.
75. Wong R, Cunningham D. 2008. Using predictive biomarkers to select patients with advanced colorectal cancer for treatment with epidermal growth factor receptor antibodies. J Clin Oncol 26:5668-5670.
76. Yang J, Weinberg RA. 2008. Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell 14:818-829.
77. Yoshida T, Okamoto I, Okabe T, Iwasa T, Satoh T, Nishio K, Fukuoka M, Nakagawa K. 2008. Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk. Int J Cancer 122:1530-1538.