STAT3 and epithelial–mesenchymal transitions in carcinomas

Abstract

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.

The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation

“…Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human malignancies, including head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers (27)(28)(29). Aberrantly STAT3 activation contributes to oncogenesis by preventing apoptosis, inducing cell proliferation, angiogenesis, invasion, and metastasis as well as suppressing antitumor immune responses (30,31).…”

Inhibition of the autocrine IL-6–JAK2–STAT3–calprotectin axis as targeted therapy for HR−/HER2+breast cancers

“…Activation of STAT3 in metastatic progression is well established and has been associated with myeloid cell recruitment (Chang et al 2013), angiogenesis (Chang et al 2013), epithelial-mesenchymal transition (Wendt et al 2014), and migration (Barbieri et al 2010a). However, its potential role in the maintenance of breast cancer cell homeostasis is not clear.…”

The JAK/STAT signaling cascade in gastric carcinoma (Review)

“…In particular, STAT3 mediates its pro-survival functions via Survivin, which not only prevents apoptosis but also promotes the mitogenic activity of cells (73,74). Studies have also shown that STAT3 controls the expression of the master EMT (epithelial-to-mesenchymal) transcriptional regulators, thus, contributing to the process of metastasis in cancers (75). An aberrant expression of STAT3 was also shown to contribute to the tumor progression via facilitating cell motility and invasion (76).…”