HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Caveolin-1 mediates chemoresistance in breast cancer stem cells via β-catenin/ABCG2 signaling pathway.

Abstract
Accumulating evidence has suggested that cancer stem cells (CSCs) are at the root of drug resistance, and recent studies have indicated that caveolin-1, a membrane transporter protein, is involved in the regulation of cancer chemoresistance and stem cell signaling. However, the current understanding of the role of caveolin-1 in breast cancer development remains controversial. Herein, we demonstrate that caveolin-1 expression was upregulated after breast cancer chemotherapy in vitro and in vivo, accompanied by co-overexpression of β-catenin and ATP-binding cassette subfamily G member 2 (ABCG2) signaling. Additionally, breast CSCs were enriched for caveolin-1 expression. Caveolin-1 silencing sensitized breast CSCs by limiting their self-renewal ability but promoting the differentiation process. β-catenin silencing prevented the enhanced chemoresistance of CSCs induced by caveolin-1 overexpression, indicating that β-catenin is an essential molecule responsible for caveolin-1-mediated action. Further mechanistic investigation revealed that caveolin-1 silencing could downregulate the β-catenin/ABCG2 pathway through glycogen synthase kinase 3 beta activation and Akt inhibition, resulting in increased β-catenin phosphorylation and proteasomal degradation. Clinical investigation also revealed a close correlation between caveolin-1 and β-catenin/ABCG2 signaling in breast cancer samples. Notably, caveolin-1 was highly elevated in triple-negative breast cancer, and caveolin-1 silencing significantly impaired the tumorigenicity and chemoresistance of breast CSCs in in vivo models. Overall, our study not only highlights the role of caveolin-1 in mediating the chemoresistance of breast CSCs via β-catenin/ABCG2 regulation but also provides novel approaches for future therapies targeting CSCs.
AuthorsZhiyu Wang, Neng Wang, Wenping Li, Pengxi Liu, Qianjun Chen, Honglin Situ, Shaowen Zhong, Li Guo, Yi Lin, Jiangang Shen, Jianping Chen
JournalCarcinogenesis (Carcinogenesis) Vol. 35 Issue 10 Pg. 2346-56 (Oct 2014) ISSN: 1460-2180 [Electronic] England
PMID25085904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Chemical References
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • CAV1 protein, human
  • Caveolin 1
  • Neoplasm Proteins
  • beta Catenin
Topics
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters (metabolism)
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Breast Neoplasms (drug therapy, metabolism, pathology)
  • Caveolin 1 (genetics, metabolism)
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm (drug effects, genetics)
  • Female
  • Humans
  • Mice, Nude
  • Neoplasm Proteins (metabolism)
  • Neoplastic Stem Cells (drug effects, metabolism)
  • Xenograft Model Antitumor Assays
  • beta Catenin (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: