The phosphoinositide-binding protein TRAF4 modulates tight junction stability and migration of cancer cells

Adrien Rousseau, Léa P. Wilhelm, Catherine Tomasetto, Fabien Alpy

Research output: Contribution to journalComment/debate

4 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4), a protein localized in TJs in normal epithelial cells, is frequently overexpressed in carcinomas. We recently found that TRAF4 impedes TJ formation/stability and favors cell migration, 2 hallmarks of cancer progression. In addition TRAF4 contributes to the TGFβ-induced epithelial-mesenchymal transition (EMT), metastasis, and p53 destabilization. TRAF4 recruitment to TJs is a prerequisite for its biological function on TJ formation/stability and on cell migration. Interestingly, TRAF4 is targeted to TJs through lipid-binding. The trimeric TRAF domain of TRAF4 binds 3 phosphoinositide (PIP) molecules. These findings shed new light on the role of TRAF4 in cancer progression; they provide a novel link between lipid metabolism and cancer progression and support the notion that TRAF4 could be a relevant target for cancer therapies. TRAF4 belongs to a family of 7 human proteins involved in different biological processes, such as inflammation, immunity and embryonic development. While the lipid-binding ability of the TRAF domain is conserved among the whole TRAF protein family, its functional role remains to be established for the remaining TRAF proteins.

Original languageEnglish
Article numbere975597
Number of pages6
JournalTissue Barriers
Volume2
Issue number4
Early online date14 Nov 2014
DOIs
Publication statusPublished - 2014

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Keywords

  • Breast cancer
  • Cell migration
  • Phosphoinositide
  • Tight junction
  • TRAF domain

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