TRIM28 promotes luminal cell plasticity in a mouse model of prostate cancer

Authors

Ashutosh S. Yende, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Emily C. Williams, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Andrew Pletcher, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Alexandra Helfand, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Helen Ibeawuchi, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Tanya M. North, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Patricia S. Latham, The George Washington University Cancer Center, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Anelia Horvath, The George Washington University Cancer Center, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Maho Shibata, Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA. mshibata@gwu.edu.

Document Type

Journal Article

Publication Date

3-8-2023

Journal

Oncogene

DOI

10.1038/s41388-023-02655-0

Abstract

The Tripartite motif-containing 28 (TRIM28) transcriptional cofactor is significantly upregulated in high-grade and metastatic prostate cancers. To study the role of TRIM28 in prostate cancer progression in vivo, we generated a genetically-engineered mouse model, combining prostate-specific inactivation of Trp53, Pten and Trim28. Trim28 inactivated NPp53T mice developed an inflammatory response and necrosis in prostate lumens. By conducting single-cell RNA sequencing, we found that NPp53T prostates had fewer luminal cells resembling proximal luminal lineage cells, which are cells with progenitor activity enriched in proximal prostates and prostate invagination tips in wild-type mice with analogous populations in human prostates. However, despite increased apoptosis and reduction of cells expressing proximal luminal cell markers, we found that NPp53T mouse prostates evolved and progressed to invasive prostate carcinoma with a shortened overall survival. Altogether, our findings suggest that TRIM28 promotes expression of proximal luminal cell markers in prostate tumor cells and provides insights into TRIM28 function in prostate tumor plasticity.

APA Citation

Yende, Ashutosh S.; Williams, Emily C.; Pletcher, Andrew; Helfand, Alexandra; Ibeawuchi, Helen; North, Tanya M.; Latham, Patricia S.; Horvath, Anelia; and Shibata, Maho, "TRIM28 promotes luminal cell plasticity in a mouse model of prostate cancer" (2023). GW Authored Works. Paper 2604.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2604

Department

Anatomy and Regenerative Biology