Multifunctional role of PED/PEA15 in cell death and cell motility in human non small cell lung cancer (NSCLC)

Abstract

PED (phosphoprotein enriched in diabetes) is a 15 KDa protein involved in many cellular pathways and human diseases, including type II diabetes and cancer. We recently reported its overexpression in breast and lung cancers, and B-cell chronic lymphocytic leukemia (B-CLL). Furthermore, PED mediated resistance to chemotherapic agents in breast cancer cell lines and TRAIL (TNF-Related Apoptosis Inducing Ligand) treatment in primary B-CLL cells and lung cancer cell lines. Then, we show that PED function and expression are reguated by vitamin D3. To better understand its role in cancer, we focused on PED interactome characterization in non small cell lung cancer (NSCLC) cell line, A459. By the Tandem Affinity Purification (TAP), we have identified Rac1, member of mammalian Rho GTPase proteins family, as a PED-interacting protein, which is involved in many cellular processes, such as migration and invasion. Here we show that PED stimulates migration and invasion in Rac1-dependent manner in non small cell lung cancer. In conclusion, this is teh first report showing that PED and Rac1 interact and that this interaction regulates cell migration/invasion process through ERK1/2 pathway.