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

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 TR...

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Bibliographic Details
Published in:Tissue barriers 2014-01, Vol.2 (4), p.e975597-e975597
Main Authors: Rousseau, Adrien, Wilhelm, Léa P, Tomasetto, Catherine, Alpy, Fabien
Format: Article
Language:English
Subjects:
breast cancer
Cancer
cell migration
Cellular Biology
EMT, epithelial-mesenchymal transition
Life Sciences
MEC, mammary epithelial cell
phosphoinositide
PIP, phosphoinositide
TGF-β, transforming growth factor β
tight junction
TJ, tight junction
TRAF domain
TRAF4, tumor necrosis factor (TNF) receptor-associated factor 4
ZF, zinc finger
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Summary: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 TGF-β-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.
ISSN:2168-8362
2168-8370
2168-8370
DOI:10.4161/21688370.2014.975597