Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer

Date:	28 August 2024
PMID:	PMC11358296
Category:	N/A
Authors:	Mindy K Graham, Rulin Wang, Roshan Chikarmane, Bulouere Abel, Ajay Vaghasia, Anuj Gupta, Qizhi Zheng, Jessica Hicks, Polina Sysa-Shah, Xin Pan, Nicole Castagna, Jianyong Liu, Jennifer Meyers, Alyza Skaist, Yan Zhang, Michael Rubenstein, Kornel Schuebel, Brian W Simons, Charles J Bieberich, William G Nelson, Shawn E Lupold, Theodore L DeWeese, Angelo M De Marzo, Srinivasan Yegnasubramanian
Abstract:

How prostate cancer cells and their precursors mediate changes in the tumor microenvironment (TME) to drive prostate cancer progression is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we perform extensive single-cell RNA-sequencing (scRNA-seq) and molecular pathology of the comparative biology between human prostate cancer and key stages in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues reveal that cancer cell-intrinsic activation of MYC signaling is a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Cell communication network and pathway analyses in GEMMs show that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogram the TME during carcinogenesis, leading to a convergence of cell state alterations in neighboring epithelial, immune, and fibroblast cell types that parallel key findings in human prostate cancer.

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Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.

The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:

Project Number:	Awardee Organization
U54CA274374	Fred Hutchinson Cancer Center
U54CA274375	Houston Methodist Research Institute
U54CA274370	Johns Hopkins University
U54CA274371	UT MD Anderson Cancer Center
U54CA274367	Vanderbilt University Medical Center