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STAT3 is a master regulator of epithelial identity and KRAS-driven tumorigenesis

Stephen D'Amico1, Jiaqi Shi2, Benjamin L Martin3

  • 1Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794, USA.

Genes & Development
|August 24, 2018
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) plays a dual role in cancer. This study reveals STAT3 maintains epithelial cell identity, with its phosphorylation level dictating tumor progression in KRAS-driven cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Signal transducer and activator of transcription 3 (STAT3) exhibits contradictory roles in cancer, acting as both essential and suppressive.
  • The context-dependent functions of STAT3 necessitate further investigation into its underlying mechanisms in tumorigenesis.

Purpose of the Study:

  • To elucidate the mechanisms of STAT3 function in KRAS-driven lung and pancreatic cancers.
  • To define the role of STAT3 in maintaining epithelial cell identity and differentiation within the context of cancer.

Main Methods:

  • Evaluation of STAT3 activity in KRAS-driven lung and pancreatic cancer models.
  • Analysis of the impact of STAT3 loss versus persistent activation on cellular phenotypes and tumor behavior.

Main Results:

  • STAT3 is crucial for maintaining epithelial cell identity and differentiation.
  • Loss of STAT3 correlates with mesenchymal phenotypes and aggressive tumor progression.
  • Persistent STAT3 activation via Tyr705 phosphorylation promotes differentiated epithelial morphology and influences tumorigenic potential.

Conclusions:

  • STAT3's function in cancer is context-dependent, particularly concerning its phosphorylation status.
  • Quantitative differences in STAT3 Tyr705 phosphorylation dictate distinct outcomes in tumor progression, impacting epithelial-mesenchymal transition and tumor aggressiveness.
Keywords:
context specificityepithelial carcinogenesisinflammationmetastasis

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