PED interacts with Rac1 and regulates cell migration/invasion processes in human non-small cell lung cancer cells

Journal of Cellular Physiology
Ciro ZancaGerolama Condorelli

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 that PED is overexpressed in human cancers and mediates resistance to induced apoptosis. To better understand its role in cancer, we investigated on PED interactome in non-small cell lung cancer (NSCLC). By the Tandem Affinity Purification (TAP), we identified and characterized among others, Rac1, a member of mammalian Rho GTPase protein family, as PED-interacting protein. In this study we show that PED coadiuvates Rac1 activation by regulating AKT mediated Rac1-Ser(71) phosphorylation. Furthermore, we show that the expression of a constitutively active Rac, affected PED-Ser(104) phosphorylation, which is important for PED-regulated ERK 1/2 nuclear localization. Through specific Rac1-siRNA or its pharmacological inhibition, we demonstrate that PED augments migration and invasion in a Rac1-dependent manner in NSCLC. In conclusion, we show for the first time that PED and Rac1 interact and that this interaction modulates cell migration/invasion processes in cancer cells through ERK1/2 pathway.

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Citations

Mar 25, 2014·Pharmacology & Therapeutics·Fiona H Greig, Graeme F Nixon
Apr 26, 2016·Molecular Therapy. Nucleic Acids·Margherita IaboniGerolama Condorelli
Sep 8, 2011·Journal of Cellular and Molecular Medicine·Pietro FormisanoNunzia Montuori
Oct 30, 2016·Clinical Genetics·T ZouZ Liu
Apr 12, 2017·Expert Opinion on Therapeutic Targets·Francesca FioryFrancesco Beguinot
Jan 31, 2014·Journal of Cellular Physiology·Cristina QuintavalleGerolama Condorelli

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