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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.

 

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

Related Products

Cat.No. Product Name Information
S1105 LY294002 LY294002 (SF 1101, NSC 697286) is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. LY294002 also inhibits CK2 with IC50 of 98 nM. LY294002 is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
S1177 PD98059 PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM in a cell-free assay, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2. PD98059 is a ligand for the aryl hydrocarbon receptor (AHR) and functions as an AHR antagonist.

Related Targets

PI3K