Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta

Yunting Jian, Lingzhi Kong, Hongyi Xu, Xinjian Huang, Yue Li, Dongni Shi, Yunyun Xiao, Muwen Yang, Siqi Li, Xiangfu Chen, Ying Ouyang, Yameng Hu, Xin Chen, Pian Liu, View ORCID ProfileWeidong Wei
doi: https://doi.org/10.1101/2021.05.09.443305
Yunting Jian
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lingzhi Kong
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hongyi Xu
2Department of Breast Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xinjian Huang
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yue Li
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dongni Shi
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yunyun Xiao
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Muwen Yang
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Siqi Li
2Department of Breast Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiangfu Chen
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ying Ouyang
1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yameng Hu
3Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xin Chen
4Departments of Pathophysiology, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pian Liu
5Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: weiwd@sysucc.org.cn liupianamazing@126.com
Weidong Wei
2Department of Breast Surgery, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Weidong Wei
  • For correspondence: weiwd@sysucc.org.cn liupianamazing@126.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The majority of clinical deaths among patients with triple-negative breast cancer (TNBC) are caused by uncontrolled cell proliferation and aggressive metastases, which is regulated by hyperactive glycogen synthase kinase 3 beta (GSK3β); however, the underlying mechanisms remain largely unknown. In the present study, we found that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) was specifically upregulated in TNBC, compared with that in normal tissues and non-TNBC. High PPP1R14C expression correlated significantly with shorter 5-year relapse-free survival and overall survival in patients with TNBC. Overexpressing PPP1R14C promoted, while suppression of PPP1R14C decreased the cell proliferation and the aggressive phenotype of TNBC cells, in vitro and in vivo. Importantly, we revealed that PPP1R14C interacted with and inactivated type 1 Ser/Thr protein phosphatase (PP1) to sustain GSK3β phosphorylation at S9, and induced the ubiquitylation and degradation of non-phosphorylated GSK3β (S9A) via recruiting E3 ligase, TRIM25. Furthermore, treating with C2 ceramide (C2), which recovered kinase activity of GSK3β, resulted in tumor growth inhibition in PPP1R14C-overexpressing TNBC cells. Our findings reveal a novel mechanism whereby PPP1R14C sustains inactive GSK3β, which might lead to targeted therapy for TNBC.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding This work was supported by the National Natural Science Foundation of China [grant numbers 81772800, 82072945, 82003052, 82003128 and 81802405]; the Natural Science Foundation of Guangdong Province [grant numbers 2020A1515010260]; and the China Postdoctoral Science Foundation [grant number 2019M663290].

  • Competing Interests The authors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted May 10, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta
Yunting Jian, Lingzhi Kong, Hongyi Xu, Xinjian Huang, Yue Li, Dongni Shi, Yunyun Xiao, Muwen Yang, Siqi Li, Xiangfu Chen, Ying Ouyang, Yameng Hu, Xin Chen, Pian Liu, Weidong Wei
bioRxiv 2021.05.09.443305; doi: https://doi.org/10.1101/2021.05.09.443305
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta
Yunting Jian, Lingzhi Kong, Hongyi Xu, Xinjian Huang, Yue Li, Dongni Shi, Yunyun Xiao, Muwen Yang, Siqi Li, Xiangfu Chen, Ying Ouyang, Yameng Hu, Xin Chen, Pian Liu, Weidong Wei
bioRxiv 2021.05.09.443305; doi: https://doi.org/10.1101/2021.05.09.443305

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3607)
  • Biochemistry (7581)
  • Bioengineering (5529)
  • Bioinformatics (20809)
  • Biophysics (10338)
  • Cancer Biology (7988)
  • Cell Biology (11647)
  • Clinical Trials (138)
  • Developmental Biology (6611)
  • Ecology (10217)
  • Epidemiology (2065)
  • Evolutionary Biology (13630)
  • Genetics (9550)
  • Genomics (12854)
  • Immunology (7925)
  • Microbiology (19555)
  • Molecular Biology (7668)
  • Neuroscience (42147)
  • Paleontology (308)
  • Pathology (1258)
  • Pharmacology and Toxicology (2203)
  • Physiology (3269)
  • Plant Biology (7051)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1952)
  • Systems Biology (5429)
  • Zoology (1119)