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Clin Res Hepatol Gastroenterol. 2011 Sep;35(8-9):534-8. doi: 10.1016/j.clinre.2011.03.015. Epub 2011 Jul 22.

Pinworm and TNKS inhibitors, an eccentric duo to derail the oncogenic WNT pathway.

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Inserm U938, Laboratory of Cancer Biology and Therapeutics, UMPC Paris-6, Saint-Antoine Hospital, Kourisky building, 184, rue du Faubourg-Saint-Antoine, 75571 Paris cedex 12, France.


The WNT/β-catenin pathway underlies many human cancers through mutations in the APC, β-catenin, and Axin genes. Activation of WNT signalling can also occur due to the localization of glycogen synthase kinase 3β(GSK3β) to the multivesicular bodies, which prevents the degradation of β-catenin. This leads to accumulation of β-catenin within the cytoplasmic matrix and nucleus of cancer cells, which triggers the transactivation of genes involved in cell proliferation, including various oncogenes. Recent research into the mechanistic regulations of molecule homeostasis and identification of new small-targeted inhibitors has provided further insights into the WNT signalling pathway and its role in human cancers. Novel WNT inhibitors target unsuspected cellular enzymes, such as tankyrases, or casein kinase 1α/γ, which controls the destruction of β-catenin and GSK3β. These could lead to the identification of new biomarkers and WNT-targeted inhibitors for the treatment of cancer.

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