Cancers 2014, 6(2), 958-968; doi:10.3390/cancers6020958
STAT3 Activity and Function in Cancer: Modulation by STAT5 and miR-146b
Department of Medical Oncology, Dana-Farber Cancer Institute, and Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA
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These authors contributed equally to this work.
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Received: 24 January 2014 / Revised: 19 March 2014 / Accepted: 28 March 2014 / Published: 23 April 2014
(This article belongs to the Special Issue STAT3 Signalling in Cancer: Friend or Foe)
Abstract
The transcription factor STAT3 regulates genes that control critical cellular processes such as proliferation, survival, pluripotency, and motility. Thus, under physiological conditions, the transcriptional function of STAT3 is tightly regulated as one part of a complex signaling matrix. When these processes are subverted through mutation or epigenetic events, STAT3 becomes highly active and drives elevated expression of genes underlying these phenotypes, leading to malignant cellular behavior. However, even in the presence of activated STAT3, other cellular modulators can have a major impact on the biological properties of a cancer cell, which is reflected in the clinical behavior of a tumor. Recent evidence has suggested that two such key modulators are the activation status of other STAT family members, particularly STAT5, and the expression of STAT3-regulated genes that are part of negative feedback circuits, including microRNAs such as miR-146b. With attention to these newly emerging areas, we will gain greater insight into the consequence of STAT3 activation in the biology of human cancers. In addition, understanding these subtleties of STAT3 signaling in cancer pathogenesis will allow the development of more rational molecular approaches to cancer therapy.Keywords:
signal transduction; gene transcription; molecular oncology
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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MDPI and ACS Style
Walker, S.R.; Xiang, M.; Frank, D.A. STAT3 Activity and Function in Cancer: Modulation by STAT5 and miR-146b. Cancers 2014, 6, 958-968.