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Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition.

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.

SUBMITTER: Chiu WT

PROVIDER: S-EPMC4170798 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition.

Chiu Wen-Tai WT Lee Hsueh-Te HT Huang Feng-Ju FJ Aldape Kenneth D KD Yao Jun J Steeg Patricia S PS Chou Cheng-Yang CY Lu Zhimin Z Xie Keping K Huang Suyun S

Cancer research 20110527 14

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 we ...[more]

PMID: 21622714

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Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition.

Publications

Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition.

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