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

First Author  Graham MK Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  7414
PubMed ID  39198404 Mgi Jnum  J:353581
Mgi Id  MGI:7715932 Doi  10.1038/s41467-024-51450-2
Citation  Graham MK, et al. (2024) Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer. Nat Commun 15(1):7414
abstractText  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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