STAT3 is a Genetic Modifier of TGF-beta Induced EMT in KRAS Mutant Pancreatic Cancer

Overview

Journal Elife

Specialty Biology

Date 2024 Apr 4

PMID 38573819

Authors

Stephen DAmico

Varvara Kirillov

Oleksi Petrenko

Nancy C Reich

Affiliations

Soon will be listed here.

Abstract

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established. Here, we identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition. Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. Functional classification of the STAT3-responsive program reveals its major role in tumor maintenance and epithelial homeostasis. The signatures of STAT3-activated cell states can be projected onto human KRAS mutant tumors, suggesting that they faithfully reflect characteristics of human disease. These observations have implications for therapeutic intervention and tumor aggressiveness.

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PMID: 39001987 DOI: 10.1007/s12032-024-02443-0.

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