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PED interacts with Rac1 and regulates cell migration/invasion processes in human non‐small cell lung cancer cells
Author(s) -
Zanca Ciro,
Cozzolino Flora,
Quintavalle Cristina,
Di Costanzo Stefania,
RicciVitiani Lucia,
Santoriello Margherita,
Monti Maria,
Pucci Piero,
Condorelli Gerolama
Publication year - 2010
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22197
Subject(s) - rac1 , phosphoprotein , biology , cancer cell , protein kinase b , microbiology and biotechnology , phosphorylation , cancer research , mapk/erk pathway , cell migration , cell growth , cell , cancer , signal transduction , biochemistry , genetics
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. J. Cell. Physiol. 225: 63–72, 2010. © 2010 Wiley‐Liss, Inc.