Switching On the Evolutionary Potential of Pancreatic Cancer: The Tumor Suppressor Functions of PBRM1

Authors

Luigi Perelli
Giannicola Genovese

Publication Date

6-2-2025

Journal

Journal of Clinical Investigation

DOI

10.1172/JCI193205

PMID

40454477

PMCID

PMC12126216

PubMedCentral® Posted Date

6-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Cell plasticity is a hallmark of cancer, enabling tumor cells to acquire multiple phenotypes responsible for tumor progression, metastasis, and therapy resistance. In this issue of the JCI, Kawai and colleagues leveraged genetically engineered mouse models (GEMM) of pancreatic ductal adenocarcinoma (PDAC) to demonstrate that loss of Pbrm1, a member of the SWI/SNF complex, drives dedifferentiation and aggressive tumor features. Pbrm1 loss activated a program of epithelial-to-mesenchymal transition (EMT) and allowed the emergence of poorly differentiated histologies that are commonly associated with high recurrence rate and dismal prognosis. These findings reveal the role of the SWI/SNF complex during PDAC evolution in maintaining cell identity and restraining the progression of this lethal disease.

Keywords

Pancreatic Neoplasms, Animals, Humans, Mice, Carcinoma, Pancreatic Ductal, Transcription Factors, Epithelial-Mesenchymal Transition, DNA-Binding Proteins, Nuclear Proteins, Tumor Suppressor Proteins

Published Open-Access

yes

Recommended Citation

Luigi Perelli and Giannicola Genovese, "Switching On the Evolutionary Potential of Pancreatic Cancer: The Tumor Suppressor Functions of PBRM1" (2025). Faculty, Staff and Student Publications. 4427.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4427