STAT3 and epithelial-mesenchymal transitions in carcinomas.
Cellular programs coupled to cycles of epithelial-mesenchymal transitions (EMTs) play critical roles during embryogenesis, as well as during tissue development, remodeling, and repair. Research over the last decade has established the importance of an ever-expanding list of master EMT transcription factors, whose activity is regulated by STAT3 and function to stimulate the rapid transition of cells between epithelial and mesenchymal phenotypes. Importantly, inappropriate reactivation of embryonic EMT programs in carcinoma cells underlies their metastasis to distant organ sites, as well as their acquisition of stem cell-like and chemoresistant phenotypes operant in eliciting disease recurrence. Thus, targeted inactivation of master EMT transcription factors may offer new inroads to alleviate metastatic disease. Here we review the molecular, cellular, and microenvironmental factors that contribute to the pathophysiological activities of STAT3 during its regulation of EMT programs in human carcinomas.
Department of Medicinal Chemistry and Molecular Pharmacology; Purdue University; West Lafayette, IN USA.
Michael K
MK
Wendt
Department of Physiology and Biophysics; Case Western Reserve University; Cleveland, OH USA.
Nikolas
N
Balanis
Department of Molecular Biology and Microbiology; Case Western Reserve University; Cleveland, OH USA.
Cathleen R
CR
Carlin
Case Comprehensive Cancer Center, Case Western Reserve University; Cleveland, OH USA.
William P
WP
Schiemann
EGFR; EMP; EMT; STAT3; TGF-β; extracellular matrix; metastasis; signal transduction; tumor microenvironment