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Journal of Biological Chemistry
Article . 2011 . Peer-reviewed
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Journal of Biological Chemistry
Article
License: CC BY
Data sources: UnpayWall
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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

Authors: Marylynn, Snyder; Xin-Yun, Huang; J Jillian, Zhang;

Signal Transducers and Activators of Transcription 3 (STAT3) Directly Regulates Cytokine-induced Fascin Expression and Is Required for Breast Cancer Cell Migration

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.

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Keywords

STAT3 Transcription Factor, Interleukin-6, Microfilament Proteins, NF-kappa B, Antineoplastic Agents, Breast Neoplasms, Mammary Neoplasms, Animal, Oncostatin M, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Mice, Cell Movement, Cell Line, Tumor, Animals, Humans, Female, Neoplasm Metastasis, Carrier Proteins, Cell Proliferation

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    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
81
Top 10%
Top 10%
Top 10%
gold