Involvement of Erk1/2 pathway in the migration of colon cancer cells induced by PTHrP

CALVO N; CARRIERE P; MARTIN MJ; RUSSO DE BOLAND A; GENTILI C

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2014

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

Parathyroid Hormone-related Peptide (PTHrP) is implicated in several human cancers such as colon carcinoma. The pathogenesis of this disease involves several processes, including enhanced cell survival, proliferation, migration and angiogenesis. Migration of cancer cells is the crucial step in the complex process of metastasis. Recently we obtained evidence that in Caco-2 cells, a cell line from human colorectal adenocarcinoma, exogenous PTHrP increases the number of live cells and cell cycle progression via Erk1/2, p38 MAPK and PI3-kinase. The aim of our study was to investigate the role of PTHrP on migration and angiogenesis of these tumor cells. Wound healing results revealed that cell migration increased after PTHrP treatment for 24 h. Furthermore, western blot showed that the hormone (1 h) induced threonine/serine phosphorylation of p90 ribosomal S6 kinase (RSK), an enzyme recently involved in cell motility. In addition, inhibition of Erk1/2 reversed the phosphorylation of RSK and cell migration induced by PTHrP. Finally, using real-time PCR, we observed that the expression of the pro-angiogenic VEGF increased by PTHrP treatment (20 h). Taken together, our results indicate that PTHrP induces the phosphorylation of RSK and cell migration via the Erk1/2 pathway and suggest a potential role of the hormone on tumor angiogenesis.