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Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration.
J Biol Chem. 2011 Nov 11; 286(45):38886-93.JB

Abstract

The cytokines oncostatin M (OSM) and IL-6 promote breast cancer cell migration and metastasis. Both cytokines activate STAT3, a member of the STAT (signal transducers and activators of transcription) family of transcription factors. Through transcriptional regulation of its target genes, STAT3 controls a wide range of cellular processes, including cellular proliferation, oncogenesis, and cancer metastasis. Fascin is an actin-bundling protein involved in cell migration. Elevated levels of fascin expression are found in many metastatic cancers, and inhibition of fascin function by small chemical compounds leads to a block of tumor metastasis. In this work, we demonstrate that fascin is a direct STAT3 target gene in response to OSM and IL-6 in both mouse and human breast cancer cells. We show that NFκB also binds to the fascin promoter in response to cytokine treatment and this binding is STAT3-dependent. Both STAT3 and NFκB are required for the cytokine-induced expression of fascin in cancer cells. Furthermore, we demonstrate that STAT3, in directly controlling fascin expression, is both necessary and sufficient for breast cancer cell migration.

Authors+Show Affiliations

Department of Physiology and Biophysics, Cornell University Weill Medical College, New York, New York 10065, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21937440

Citation

Snyder, Marylynn, et al. "Signal Transducers and Activators of Transcription 3 (STAT3) Directly Regulates Cytokine-induced Fascin Expression and Is Required for Breast Cancer Cell Migration." The Journal of Biological Chemistry, vol. 286, no. 45, 2011, pp. 38886-93.
Snyder M, Huang XY, Zhang JJ. Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration. J Biol Chem. 2011;286(45):38886-93.
Snyder, M., Huang, X. Y., & Zhang, J. J. (2011). Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration. The Journal of Biological Chemistry, 286(45), 38886-93. https://doi.org/10.1074/jbc.M111.286245
Snyder M, Huang XY, Zhang JJ. Signal Transducers and Activators of Transcription 3 (STAT3) Directly Regulates Cytokine-induced Fascin Expression and Is Required for Breast Cancer Cell Migration. J Biol Chem. 2011 Nov 11;286(45):38886-93. PubMed PMID: 21937440.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration. AU - Snyder,Marylynn, AU - Huang,Xin-Yun, AU - Zhang,J Jillian, Y1 - 2011/09/20/ PY - 2011/9/23/entrez PY - 2011/9/23/pubmed PY - 2011/12/28/medline SP - 38886 EP - 93 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 286 IS - 45 N2 - The cytokines oncostatin M (OSM) and IL-6 promote breast cancer cell migration and metastasis. Both cytokines activate STAT3, a member of the STAT (signal transducers and activators of transcription) family of transcription factors. Through transcriptional regulation of its target genes, STAT3 controls a wide range of cellular processes, including cellular proliferation, oncogenesis, and cancer metastasis. Fascin is an actin-bundling protein involved in cell migration. Elevated levels of fascin expression are found in many metastatic cancers, and inhibition of fascin function by small chemical compounds leads to a block of tumor metastasis. In this work, we demonstrate that fascin is a direct STAT3 target gene in response to OSM and IL-6 in both mouse and human breast cancer cells. We show that NFκB also binds to the fascin promoter in response to cytokine treatment and this binding is STAT3-dependent. Both STAT3 and NFκB are required for the cytokine-induced expression of fascin in cancer cells. Furthermore, we demonstrate that STAT3, in directly controlling fascin expression, is both necessary and sufficient for breast cancer cell migration. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/21937440/Signal_transducers_and_activators_of_transcription_3__STAT3__directly_regulates_cytokine_induced_fascin_expression_and_is_required_for_breast_cancer_cell_migration_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=21937440 DB - PRIME DP - Unbound Medicine ER -