Balanis Nikolas, Carlin Cathleen R
Departments of Physiology and Biophysics, USA; Molecular Biology and Microbiology, USA.
Departments of Physiology and Biophysics, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
Mol Cell Endocrinol. 2017 Aug 15;451:24-30. doi: 10.1016/j.mce.2017.01.013. Epub 2017 Jan 12.
Elevated STAT3 activity is a hallmark of many epithelial carcinomas particularly in breast cancers where it is known to contribute to tumor progression through a variety of context-dependent biological responses. However, its role downstream of stress-exposed EGF receptors (EGFR) that are transactivated in endosomes independent of exogenous ligand has not been studied. This review discusses how STAT3 signaling induced by therapeutic stress in EGFR-driven triple-negative breast cancers (TNBC) might override normal epithelial homeostatic mechanisms and provide a survival advantage for tumor cells before they leave the primary tumor and spread to distant sites. Despite continued improvements in breast cancer treatment strategies, TNBC is still associated with poor prognosis and high risk of distant recurrence and death. Understanding EGFR-STAT3 signaling mechanisms regulating the earliest steps of tumor progression is a key to discovery of new targeted therapies against TNBC.
STAT3活性升高是许多上皮癌的一个标志，尤其是在乳腺癌中，已知它通过多种依赖于上下文的生物学反应促进肿瘤进展。然而，其在应激暴露的表皮生长因子受体（EGFR）下游的作用尚未得到研究，这些受体在内体中被反式激活，且不依赖于外源性配体。本综述讨论了在EGFR驱动的三阴性乳腺癌（TNBC）中，治疗应激诱导的STAT3信号传导如何可能超越正常上皮稳态机制，并在肿瘤细胞离开原发肿瘤并扩散到远处部位之前为其提供生存优势。尽管乳腺癌治疗策略不断改进，但TNBC仍然与预后不良以及远处复发和死亡的高风险相关。了解调节肿瘤进展最早步骤的EGFR-STAT3信号传导机制是发现针对TNBC的新靶向疗法的关键。
