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Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition.
Cancer Res. 2011 Jul 15; 71(14):4932-43.CR

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.

Authors+Show Affiliations

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21622714

Citation

Chiu, Wen-Tai, et al. "Caveolin-1 Upregulation Mediates Suppression of Primary Breast Tumor Growth and Brain Metastases By Stat3 Inhibition." Cancer Research, vol. 71, no. 14, 2011, pp. 4932-43.
Chiu WT, Lee HT, Huang FJ, et al. Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition. Cancer Res. 2011;71(14):4932-43.
Chiu, W. T., Lee, H. T., Huang, F. J., Aldape, K. D., Yao, J., Steeg, P. S., Chou, C. Y., Lu, Z., Xie, K., & Huang, S. (2011). Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition. Cancer Research, 71(14), 4932-43. https://doi.org/10.1158/0008-5472.CAN-10-4249
Chiu WT, et al. Caveolin-1 Upregulation Mediates Suppression of Primary Breast Tumor Growth and Brain Metastases By Stat3 Inhibition. Cancer Res. 2011 Jul 15;71(14):4932-43. PubMed PMID: 21622714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition. AU - Chiu,Wen-Tai, AU - Lee,Hsueh-Te, AU - Huang,Feng-Ju, AU - Aldape,Kenneth D, AU - Yao,Jun, AU - Steeg,Patricia S, AU - Chou,Cheng-Yang, AU - Lu,Zhimin, AU - Xie,Keping, AU - Huang,Suyun, Y1 - 2011/05/27/ PY - 2011/5/31/entrez PY - 2011/5/31/pubmed PY - 2011/10/21/medline SP - 4932 EP - 43 JF - Cancer research JO - Cancer Res. VL - 71 IS - 14 N2 - 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. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/21622714/Caveolin_1_upregulation_mediates_suppression_of_primary_breast_tumor_growth_and_brain_metastases_by_stat3_inhibition_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=21622714 DB - PRIME DP - Unbound Medicine ER -