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

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 Wnt5Ahigh 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 vivo with the potent lysosomotropic compound Lys05. Wnt5Ahigh cells were less sensitive to Lys05 and could be reverted by inducing β-catenin activity. Our results suggest the efficacy of autophagy inhibitors might be improved by taking the Wnt signature of melanoma cells into account. Cancer Res; 77(21); 5873–85. ©2017 AACR.

Source: Cancer Research - October 31, 2017 Category: Cancer & Oncology Authors: Abibatou Ndoye, Anna Budina-Kolomets, Curtis H. Kugel III, Marie R. Webster, Amanpreet Kaur, Reeti Behera, Vito W. Rebecca, Ling Li, Patricia A. Brafford, Qin Liu, Y.N. Vashisht Gopal, Michael A. Davies, Gordon B. Mills, Xiaowei Xu, Hong Wu, Meenhard Herl Tags: Tumor and Stem Cell Biology Source Type: research