FAM129B is a novel regulator of Wnt/β-catenin signal transduction in melanoma cells

F1000Research
Willliam ConradAndy J Chien

Abstract

The inability of targeted BRAF inhibitors to produce long-lasting improvement in the clinical outcome of melanoma highlights a need to identify additional approaches to inhibit melanoma growth. Recent studies have shown that activation of the Wnt/β-catenin pathway decreases tumor growth and cooperates with ERK/MAPK pathway inhibitors to promote apoptosis in melanoma. Therefore, the identification of Wnt/β-catenin regulators may advance the development of new approaches to treat this disease. In order to move towards this goal we performed a large scale small-interfering RNA (siRNA) screen for regulators of β-catenin activated reporter activity in human HT1080 fibrosarcoma cells. Integrating large scale siRNA screen data with phosphoproteomic data and bioinformatics enrichment identified a protein, FAM129B, as a potential regulator of Wnt/β-catenin signaling.  Functionally, we demonstrated that siRNA-mediated knockdown of FAM129B in A375 and A2058 melanoma cell lines inhibits WNT3A-mediated activation of a β-catenin-responsive luciferase reporter and inhibits expression of the endogenous Wnt/β-catenin target gene, AXIN2. We also demonstrate that FAM129B knockdown inhibits apoptosis in melanoma cells treated with WNT3A. These exp...Continue Reading

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Citations

Jan 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Haitao JiZhimin Lu
May 11, 2016·Proceedings of the National Academy of Sciences of the United States of America·Babita MadanMichael B Major
Sep 30, 2016·Journal of Cellular and Molecular Medicine·Sapan J PatelBayard D Clarkson
Sep 7, 2016·Cancers·Benjamin LuTerence J Van Raay
Sep 5, 2017·Cancer Biomarkers : Section a of Disease Markers·Yu LiRuirong Tu
Sep 16, 2015·Chinese Journal of Cancer·Sha HeJian Zhang
Nov 5, 2020·International Journal of Molecular Sciences·Hyunggu HahnHyoun Sook Kim

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