title: Stress-induced EGF receptor signaling through STAT3 and tumor progression in triple-negative breast cancer.
abstract: 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.
authors.affiliation: Departments of Physiology and Biophysics, USA; Molecular Biology and Microbiology, USA.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Balanis
authors.affiliation: Departments of Physiology and Biophysics, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: cathleen.carlin@case.edu.
authors.forename: Cathleen R
authors.initials: CR
authors.lastname: Carlin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012008:Recurrence; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cancer; EGF receptor; STAT3; Stress responses; Triple-negative breast