TIPE3, a new transfer protein of lipid second messengers regulates human cancer


Over half of human cancers have abnormally upregulated phosphoinositide signals. Recently, a new progress of phospholipid signaling was reported. Svethlana et al. found one of the transfer protein, TIPE3 (TNFAIP8L3), acts as a controller of phosphoinositide second messenger that promotes cancer. The article was published on Cancer Cell.


The TNFAIP8 family has been reported as regulators of tumorigenesis, a process that includes several classes of functional molecules that control cell death and growth. What Svethlana et al. found was TIPE3, one of the TNFAIP8 family members, is markedly upregulated in human cancers and cells treated with growth factors. Also, overexpressing and knocking out TIPE3 can promotes or inhibits tumorigenesis, respectively. Interestingly, they observed a reduction of TIPE3 expression level after treated cells with PI3K inhibitor LY294002 and/or the MEK-ERK pathway inhibitor PD98059,  indicating that TIPE3 may be involved in PI3K-AKT and MEK-ERK pathways. An activation effect of TIPE3 on PI3K-AKT and MEK-ERK pathways was confirmed then. Further examination showed TIPE3 can promote the generation of Ptdlns(3,4,5)P3 by PI3K. The binding of TIPE3 to phosphoinositides via TH domain is essential for TIPE3's function.


Their results reveal an important role of TPIE3, a phosphoinositide protein, in the mechanism of hyperactivating Ptdlns(3,4,5)P3 signaling pathway in cancer cells. Therefore, TIPE3 may represent a valuable target in therapeutic treatment of malignant diseases.


Cancer Cell. 2014 Oct 13;26(4):465-78.

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