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

Fingerprint

TNF Receptor-Associated Factor 4
Tight Junctions
Phosphatidylinositols
Cell Movement
Carrier Proteins
Cells
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Neoplasms
Biological Phenomena
Lipids
Epithelial-Mesenchymal Transition
Lipid Metabolism
Embryonic Development
Immunity
Proteins
Epithelial Cells

Keywords

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

Cite this

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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 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.",
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The phosphoinositide-binding protein TRAF4 modulates tight junction stability and migration of cancer cells. / Rousseau, Adrien; Wilhelm, Léa P.; Tomasetto, Catherine; Alpy, Fabien.

In: Tissue Barriers, Vol. 2, No. 4, e975597, 2014.

Research output: Contribution to journalComment/debate

TY - JOUR

T1 - The phosphoinositide-binding protein TRAF4 modulates tight junction stability and migration of cancer cells

AU - Rousseau, Adrien

AU - Wilhelm, Léa P.

AU - Tomasetto, Catherine

AU - Alpy, Fabien

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Cell migration

KW - Phosphoinositide

KW - Tight junction

KW - TRAF domain

U2 - 10.4161/21688370.2014.975597

DO - 10.4161/21688370.2014.975597

M3 - Comment/debate

AN - SCOPUS:84926619591

VL - 2

JO - Tissue Barriers

JF - Tissue Barriers

SN - 2168-8362

IS - 4

M1 - e975597

ER -