SIRT1 Promotes Proliferation and Inhibits the Senescence-like Phenotype in Human Melanoma Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Apr 19

PMID 24742694

Citations 33

Authors

Mickael Ohanna

Caroline Bonet

Karine Bille

Maryline Allegra

Irwin Davidson

Philippe Bahadoran

Jean-Philippe Lacour

Robert Ballotti

Corine Bertolotto

Affiliations

Soon will be listed here.

Abstract

SIRT1 operates as both a tumor suppressor and oncogenic factor depending on the cell context. Whether SIRT1 plays a role in melanoma biology remained poorly elucidated. Here, we demonstrate that SIRT1 is a critical regulator of melanoma cell proliferation. SIRT1 suppression by genetic or pharmacological approaches induces cell cycle arrest and a senescence-like phenotype. Gain and loss of function experiments show that M-MITF regulates SIRT1 expression, thereby revealing a melanocyte-specific control of SIRT1. SIRT1 over-expression relieves the senescence-like phenotype and the proliferation arrest caused by MITF suppression, demonstrating that SIRT1 is an effector of MITF-induced proliferation in melanoma cells. Interestingly, SIRT1 level and activity are enhanced in the PLX4032-resistant BRAF(V600E)-mutated melanoma cells compared with their sensitive counterpart. SIRT1 inhibition decreases melanoma cell growth and rescues the sensibility to PLX4032 of PLX4032-resistant BRAF(V600E)-mutated melanoma cells. In conclusion, we provide the first evidence that inhibition of SIRT1 warrants consideration as an anti-melanoma therapeutic option.

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