title: The phosphoinositide-binding protein TRAF4 modulates tight junction stability and migration of cancer cells.
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 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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Functional Genomics and Cancer Department ; Illkirch, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; Illkirch, France ; Centre National de la Recherche Scientifique (CNRS) ; Illkirch, France ; Université de Strasbourg ; Illkirch, France ; Present address: MRC Laboratory of Molecular Biology ; Cambridge, UK.
authors.forename: Adrien
authors.initials: A
authors.lastname: Rousseau
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Functional Genomics and Cancer Department ; Illkirch, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; Illkirch, France ; Centre National de la Recherche Scientifique (CNRS) ; Illkirch, France ; Université de Strasbourg ; Illkirch, France.
authors.forename: Léa P
authors.initials: LP
authors.lastname: Wilhelm
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Functional Genomics and Cancer Department ; Illkirch, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; Illkirch, France ; Centre National de la Recherche Scientifique (CNRS) ; Illkirch, France ; Université de Strasbourg ; Illkirch, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tomasetto
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC); Functional Genomics and Cancer Department ; Illkirch, France ; Institut National de la Santé et de la Recherche Médicale (INSERM) ; Illkirch, France ; Centre National de la Recherche Scientifique (CNRS) ; Illkirch, France ; Université de Strasbourg ; Illkirch, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Alpy
keywords: EMT, epithelial-mesenchymal transition; MEC, mammary epithelial cell; PIP, phosphoinositide; TGF-β, transforming growth factor β; TJ, tight junction; TRAF domain; TRAF4, tumor necrosis factor (TNF) receptor-associated factor 4; ZF, zinc finger; breast cancer; cell migration; phosphoinositide; tight junction