Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by Stat3 inhibition

Wen Tai Chiu, Hsueh Te Lee, Feng Ju Huang, Kenneth D. Aldape, Jun Yao, Patricia S. Steeg, Cheng Yang Chou, Zhimin Lu, Keping Xie, Suyun Huang

研究成果: Article

47 引文 斯高帕斯(Scopus)

摘要

Stat3 activation has been implicated as an important driver of brain metastasis in breast cancer, but the critical targets of Stat3 in this process are yet to be fully defined. In this study, we identified the lipid raft organizing protein Caveolin-1 (Cav-1) as a critical genetic target of Stat3 in this process. In human breast cancers, we found that activated Stat3 correlated with attenuation of Cav-1 in brain metastases relative to primary tumors. Cav-1 promoter activity and gene expression were increased by overexpressing an activated form of Stat3 but decreased by attenuation of Stat3 activity or expression. We identified putative Stat3-binding elements in the Cav-1 promoter and showed a direct repression of Cav-1 transcription by Stat3. Reciprocally, we showed that strategies to increase or decrease Cav-1 expression were sufficient to attenuate or promote breast cancer cell invasion. Furthermore, increased expression of Cav-1 phenocopied the effects of Stat3 activation in blocking primary tumor growth and abrogating formation of brain metastases. Collectively, our findings provide clinical and mechanistic evidence that Cav-1 is a critical target for suppression by Stat3 in driving invasion and metastasis of breast cancer cells.

原文English
頁(從 - 到)4932-4943
頁數12
期刊Cancer Research
71
發行號14
DOIs
出版狀態Published - 2011 七月 15

    指紋

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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