Signal transduction pathways associated with PTHrP-induced migration of intestinal tumor cells

CARRIERE P; CALVO N; MARTIN MJ; GENTILI C

Sierra de la Ventana

Congreso; XXXII REUNIÓN ANUAL AAOMM; 2015

AAOMM

Parathyroid Hormone-related Peptide (PTHrP) is involved in several tumors such as colon carcinoma. The pathogenesis of this disease involves several processes, including enhanced cell survival, proliferation, migration and angiogenesis. Migration of tumor cells is the crucial step in the complex process of metastasis. In this study we investigated the role of PTHrP on the migration of Caco-2 cells, a cell line from human colorectal adenocarcinoma, and the molecular mechanisms involved in this process. Wound healing results revealed that PTHrP treatment increases cell migration. Two changes occur when the cell migrates: the reorganization of the actin cytoskeleton and the formation of plasma membrane projections anchored through cell adhesion complexes that are regulated by tyrosine kinases. We performed a ?wound? in the cell monolayer followed by immunofluorescence analysis using anti-phosphotyrosine and anti-actin antibodies, and we observed in cells treated with PTHrP for 24 h the presence of many small structures that presumably corresponding to focal adhesions associated with actin filaments. The serine/threonine ribosomal S6 kinase (RSK) has recently been involved in cell migration, invasion and metastasis both in vitro and in vivo and its activation by phosphorylation may be mediated by Erk1/2. Western blot analysis revealed that PTHrP increases the phosphorylation of RSK in Caco-2 cells. In addition, using specific inhibitors we demonstrated that the Erk1/2 MAPK contributes to the phosphorylation of RSK and the migration induced by PTHrP. Taken together, our results indicate that PTHrP induces the phosphorylation of RSK and cell migration of Caco-2 cells via the Erk1/2 pathway.