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

Willliam Conrad, Michael B. Major, Michele A. Cleary, Marc Ferrer, Brian Roberts, Shane Marine, Namjin Chung, William T. Arthur, Randall T. Moon, Jason D. Berndt, Andy J. Chien

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 experiments support a role for FAM129B in linking Wnt/β-catenin signaling to apoptosis in melanoma.

Original languageEnglish
Article number134
JournalF1000Research
Volume2
Issue number1
DOIs
StatePublished - Oct 10 2013

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