ATG5 Mediates a Positive Feedback Loop between Wnt Signaling and Autophagy in Melanoma.

ABSTRACT: Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5A^high cells decreased Wnt5A and increased β-catenin. To define the physiologic relevance of this loop, melanoma cells with different Wnt status were treated in vitro and in vi

SUBMITTER: Ndoye A 

PROVIDER: S-EPMC5718045 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature