PED interacts with Rac1 and regulates cell migration/invasion processes in human non-small cell lung cancer cells.
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.
Zanca
Ciro
C
Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, Naples, Italy.
Cozzolino
Flora
F
Quintavalle
Cristina
C
Di Costanzo
Stefania
S
Ricci-Vitiani
Lucia
L
Santoriello
Margherita
M
Monti
Maria
M
Pucci
Piero
P
Condorelli
Gerolama
G
D051017:Apoptosis Regulatory Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C092039:PEA15 protein, human; D010750:Phosphoproteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020830:rac1 GTP-Binding Protein