DNMT3b Modulates Melanoma Growth by Controlling Levels of MTORC2 Component RICTOR

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2016 Mar 1

PMID 26923591

Citations 43

Authors

Goran Micevic

Viswanathan Muthusamy

William Damsky

Nicholas Theodosakis

Xiaoni Liu

Katrina Meeth

Emily Wingrove

Manjula Santhanakrishnan

Marcus Bosenberg

Affiliations

Soon will be listed here.

Abstract

DNA methyltransferase DNMT3B is frequently overexpressed in tumor cells and plays important roles during the formation and progression of several cancer types. However, the specific signaling pathways controlled by DNMT3B in cancers, including melanoma, are poorly understood. Here, we report that DNMT3B plays a pro-tumorigenic role in human melanoma and that DNMT3B loss dramatically suppresses melanoma formation in the Braf/Pten mouse melanoma model. Loss of DNMT3B results in hypomethylation of the miR-196b promoter and increased miR-196b expression, which directly targets the mTORC2 component Rictor. Loss of RICTOR in turn prevents mTORC2 activation, which is critical for melanoma formation and growth. These findings establish Dnmt3b as a regulator of melanoma formation through its effect on mTORC2 signaling. Based on these results, DNMT3B is a potential therapeutic target in melanoma.

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