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