The Diacylglycerol Kinase α/atypical PKC/β1 Integrin Pathway in SDF-1α Mammary Carcinoma Invasiveness

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jun 3

PMID 24887021

Citations 18

Authors

Elena Rainero

Cristina Cianflone

Paolo Ettore Porporato

Federica Chianale

Valeria Malacarne

Valentina Bettio

Elisa Ruffo

Michele Ferrara

Fabio Benecchia

Daniela Capello

Wolfgang Paster

Irene Locatelli

Alessandra Bertoni

Nicoletta Filigheddu

Fabiola Sinigaglia

Jim C Norman

Gianluca Baldanzi

Andrea Graziani

Affiliations

Soon will be listed here.

Abstract

Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells.

Citing Articles

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