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.