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

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4932-4943
Number of pages12
JournalCancer Research
Volume71
Issue number14
DOIs
Publication statusPublished - 2011 Jul 15

Fingerprint

Caveolin 1
Up-Regulation
Breast Neoplasms
Neoplasm Metastasis
Brain
Growth
Neoplasms
Lipids
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chiu, Wen Tai ; Lee, Hsueh Te ; Huang, Feng Ju ; Aldape, Kenneth D. ; Yao, Jun ; Steeg, Patricia S. ; Chou, Cheng Yang ; Lu, Zhimin ; Xie, Keping ; Huang, Suyun. / Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by Stat3 inhibition. In: Cancer Research. 2011 ; Vol. 71, No. 14. pp. 4932-4943.
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Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by Stat3 inhibition. / Chiu, Wen Tai; Lee, Hsueh Te; Huang, Feng Ju; Aldape, Kenneth D.; Yao, Jun; Steeg, Patricia S.; Chou, Cheng Yang; Lu, Zhimin; Xie, Keping; Huang, Suyun.

In: Cancer Research, Vol. 71, No. 14, 15.07.2011, p. 4932-4943.

Research output: Contribution to journalArticle

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