title: LoVo colon cancer cells resistant to oxaliplatin overexpress c-MET and VEGFR-1 and respond to VEGF with dephosphorylation of c-MET.
abstract: Oxaliplatin-resistant LoVo colon cancer cells overexpressing c-MET and VEGFR-1 were selected to study several signaling pathways involved in chemoresistance, as well as the effect of increasing amounts of VEGF in the regulation of c-MET. In comparison with chemosensitive LoVo colon cancer cells, oxaliplatin-resistant cells (LoVoR) overexpress and phosphorylate c-MET, upregulate the expression of transmembrane and soluble VEGFR-1 and, unexpectedly, downregulate VEGF. In addition, LoVoR cells activate other transduction pathways involved in chemoresistance such as Akt, β-catenin-TCF4 and E-cadherin. While c-MET is phosphorylated in LoVoR cells expressing low levels of VEGF, c-MET phosphorylation decreases when recombinant VEGF is added into the culture medium. Inhibition of c-MET by VEGF is mediated by VEGFR-1, since phosphorylation of c-MET in the presence of VEGF is restored after silencing VEGFR-1. Dephosphorylation of c-MET by VEGF suggests that tumors coexpressing VEGFR-1 and c-MET may activate c-MET as a result of anti-VEGF therapy.
authors: Departament de Ciències Fisiològiques I. Laboratori de Genètica Molecular, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain.
authors: Belén
authors: B
authors: Mezquita
authors: Medical Oncology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors: Estela
authors: E
authors: Pineda
authors: Departament de Ciències Fisiològiques I. Laboratori de Genètica Molecular, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors: Jovita
authors: J
authors: Mezquita
authors: Departament de Ciències Bàsiques, Universitat Internacional de Catalunya, Barcelona, Spain.
authors: Pau
authors: P
authors: Mezquita
authors: Departament de Ciències Fisiològiques I. Laboratori de Genètica Molecular, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors: Montserrat
authors: M
authors: Pau
authors: Medical Oncology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors: Jordi
authors: J
authors: Codony-Servat
authors: Medical Oncology Service, Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain.
authors: Eva
authors: E
authors: Martínez-Balibrea
authors: Departament de Medicina Experimental, Universitat de Lleida, Alcalde Rovira Roure, Lleida, Spain.
authors: Conchi
authors: C
authors: Mora
authors: Medical Oncology Department, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors: Joan
authors: J
authors: Maurel
authors: Departament de Ciències Fisiològiques I. Laboratori de Genètica Molecular, IDIBAPS, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
authors: Cristóbal
authors: C
authors: Mezquita
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D010766:Phosphorylation / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; C501162:FLT1 protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: LoVo colon cancer cells; VEGFR-1/c-MET; chemoresistance; β-catenin-TCF4E