The transforming functions of PI3-kinase-γ are linked to disruption of intercellular adhesion and promotion of cancer cell invasion

Samir Attoub, Olivier De Wever, Eric Bruyneel, Marc Mareel, Christian Gespach

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Citations (Scopus)

Abstract

The involvement of phosphoinositide 3-kinases class IA (PI3K-α and -β) in cancer cell proliferation, survival, motility, and invasiveness is now well established. However, the possible contribution of the class IB PI3Kγ in cancer cell transformation remains to be explored. In this study, we have stably transfected the PI3Kγ-deficient human colon cancer cell line HCT8/S11 with expression vectors encoding either wild-type PI3Kγ, its plasma membrane targeted form CAAX-PI3Kγ, or the PI3Kγ lipid and protein kinase-dead mutant (CAAX-K832R). We provide evidence that the constitutively active CAAX-PI3Kγ variant induced collagen type I invasion in HCT8/S11 cells through disruption of cell-cell adhesion, with no apparent impact on cell proliferation and motility. The proinvasive activity of CAAX-PI3K-γ was abolished by pharmacological inhibitors targeting PI3-K activities (wortmannin), Rho-GTPases, and the Rho-Rho kinase axis (C3T exoenzyme and Y27632, respectively). Conversely, the wild-type PI3Kγ and its double mutant CAAX-K832R were ineffective on cancer cell invasion measured under control or stimulated conditions operated with the proinvasive agents leptin and intestinal trefoil factor. Taken together, our data indicate that PI3Kγ exerts transforming functions via several mechanisms in human colon epithelial cancer cells, including alterations of homotypic cell-cell adhesion and induction of collagen type I invasion through canonical proinvasive pathways.

Original languageEnglish
Title of host publicationRecent Advances in Clinical Oncology
PublisherBlackwell Publishing Inc.
Pages204-213
Number of pages10
ISBN (Print)9781573317009
DOIs
Publication statusPublished - Sep 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1138
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Cell proliferation
  • Leptin
  • MAPK
  • Motility
  • Rho-GTPases
  • Trefoil peptides

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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