EGFR-mediated apoptosis via STAT3

Exp Cell Res. 2017 Jul 1;356(1):93-103. doi: 10.1016/j.yexcr.2017.04.016. Epub 2017 Apr 19.

Abstract

The Epidermal Growth Factor Receptor (EGFR) is a cell surface receptor with primary implications in cell growth in both normal and malignant tissue. Paradoxically, cell lines that hyperexpress the EGFR have been documented to undergo receptor-mediated apoptosis. The underlying mechanism by which EGF-induced apoptosis occurs however remains inexplicit. In an attempt to identify this mechanism, we assessed downstream effectors of EGFR in MDA-MB-468 cells during conditions of EGF-induced apoptosis. The effector assessment revealed STAT3 as a potential mediator of EGF-induced apoptosis. Alternative strategies for activating STAT3, independent of EGFR stimulation, resulted in the induction of the apoptotic pathways. A reduction in STAT3 expression via RNAi resulted in a significant attenuation of EGF-induced PARP cleavage. Our findings support STAT3 as a positive mediator of EGF-induced apoptosis in MDA-MB-468 cells.

Keywords: A431 Cells; Apoptosis; Epidermal Growth Factor Receptor; MDA-MB-468 Cells; Oncostatin M; S3I-201; STAT3; Stattic.

MeSH terms

  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Oncostatin M / genetics
  • Oncostatin M / metabolism
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / genetics*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / genetics

Substances

  • OSM protein, human
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Oncostatin M
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • EGFR protein, human
  • ErbB Receptors