Year: 2019
Type: article
Abstract: Autophagy perturbation represents an emerging therapeutic strategy in cancer. Although LATS1 and LATS2 kinases, core components of the mammalian Hippo pathway, have been shown to exert tumor suppressive activities, here we report a pro-survival role of LATS1 but not LATS2 in hepatocellular carcinoma (HCC) cells. Specifically, LATS1 restricts lethal autophagy in HCC cells induced by sorafenib, the standard of care for advanced HCC patients. Notably, autophagy regulation by LATS1 is independent of its kinase activity. Instead, LATS1 stabilizes the autophagy core-machinery component Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263 on Beclin-1. Consequently, ubiquitination of Beclin-1 negatively regulates autophagy by promoting inactive dimer formation of Beclin-1. Our study highlights a functional diversity between LATS1 and LATS2, and uncovers a scaffolding role of LATS1 in mediating a cross-talk between the Hippo signaling pathway and autophagy.
Source: Nature Communications
Authors: Fengyuan Tang, Ruize Gao, Beena Jeevan-Raj, Christof B. Wyss, Ravi K. R. Kalathur, Salvatore Piscuoglio, Charlotte K. Y. Ng, Sravanth K. Hindupur, Sandro Nuciforo, Eva Dazert, Thomas Bock, Shuang Song, David Buechel, Marco F. Morini, Alexander Hergovich, Patrick Matthias, Dae-Sik Lim, Luigi M. Terracciano, Markus H. Heim, Michael N. Hall, Gerhard Christofori
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
OpenAlex ID: W2995282383