Premium
LoVo colon cancer cells resistant to oxaliplatin overexpress c‐MET and VEGFR‐1 and respond to VEGF with dephosphorylation of c‐MET
Author(s) -
Mezquita Belén,
Pineda Estela,
Mezquita Jovita,
Mezquita Pau,
Pau Montserrat,
CodonyServat Jordi,
MartínezBalibrea Eva,
Mora Conchi,
Maurel Joan,
Mezquita Cristóbal
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22289
Subject(s) - biology , dephosphorylation , oxaliplatin , vegf receptors , cancer research , colorectal cancer , phosphorylation , medicine , c met , cancer , biochemistry , phosphatase , receptor , genetics , hepatocyte growth factor
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. © 2015 Wiley Periodicals, Inc.