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  3. LKB1/AMPK axis crosstalks with Wnt/β-catenin signaling in cancer via the deubiquitinase USP10

LKB1/AMPK axis crosstalks with Wnt/β-catenin signaling in cancer via the deubiquitinase USP10

  • FEBS Lett. 2023 Oct 24. doi: 10.1002/1873-3468.14763.
Yinuo Wang 1,  Jingwei Liu 2,  Shaoqin Zheng 1,  Liu Cao 2,  Yiwei Li 3,  Ren Sheng 1
Affiliations

Affiliations

  • 1 College of Life and Health Science, Northeastern University, Shenyang, 110819, China.
  • 2 College of Basic Medical Science, China Medical University, Shenyang, 110122, China.
  • 3 Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.
PMID: 37873736 DOI: 10.1002/1873-3468.14763
Abstract

The liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) axis pivotally controls cell metabolism and suppresses abnormal growth in various cancers. Wnt/β-catenin is a frequently dysregulated signaling pathway that drives oncogenesis. Here, we discovered a crosstalk mechanism between the LKB1/AMPK axis and Wnt/β-catenin signaling. Activated AMPK phosphorylates the Deubiquitinase USP10 to potentiate the deubiquitination and stabilization of the key scaffold protein Axin1. This phosphorylation also strengthens the binding between USP10 and β-catenin and supports the phase transition of β-catenin. Both processes suppress Wnt/β-catenin amplitude in parallel and inhibit colorectal Cancer growth in a clinically relevant manner. Collectively, we established a crosstalk route by which LKB1/AMPK regulates Wnt/β-catenin signaling in Cancer. USP10 acts as the hub in this process, thus enabling LKB1/AMPK to suppress tumor growth via regulation of both metabolism and cell proliferation.

Keywords

AMPK; LKB1; USP10; Wnt/β-catenin; cellular signaling transduction; signaling crosstalk.

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