β- catenin turnover is regulated by Nek10-mediated tyrosine phosphorylation in A549 lung adenocarcinoma cells
成果类型：
Article
署名作者：
Dutt, Previn; Haider, Nasir; Mouaaz, Samar; Podmore, Lauren; Stambolic, Vuk
署名单位：
University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-10685
DOI：
10.1073/pnas.2300606121
发表日期：
2024-05-07
关键词：
摘要：
beta- catenin has influential roles affecting embryonic development, tissue homeostasis, and human diseases including cancer. Cellular beta- catenin levels are exquisitely controlled by a variety of regulatory mechanisms. In the course of exploring the functions of the Nek10 tyrosine kinase, we observed that deletion of Nek10 in lung adenocarcinoma cells resulted in dramatic stabilization of beta- catenin, suggestive of a Nek10 role in the control of beta- catenin turnover. Nek10 - deficient cells exhibited diminished ability to form tumorspheres in suspension, grow in soft agar, and colonize mouse lung tissue following tail vein injection. Mechanistically, Nek10 associates with the Axin complex, responsible for beta- catenin degradation, where it phosphorylates beta- catenin at Tyr30, located within the regulatory region governing beta- catenin turnover. In the absence of Nek10 phosphorylation, GSK3 - mediated phosphorylation of beta- catenin, a prerequisite for its turnover, is impaired. This represents a divergent function within the Nek family, whose other members are serine - threonine kinases involved in different elements of the centrosomal cycle, primary cilia function, and DNA damage responses.