MUC16 and TP53 family co-regulate tumor-stromal heterogeneity in pancreatic adenocarcinoma.

ABSTRACT: MUC16/CA125 is one of the few oldest cancer biomarkers still used in current clinical practice. As mesothelium is an abundant source of MUC16 and a major contributor to stromal heterogeneity in PDAC, we investigated the regulation of MUC16 in tumor and stromal compartments individually. The trajectories constructed using the single-cell transcriptomes of stromal cells from KPC tumors demonstrated continuity in the trajectory path between MUC16-expressing mesothelial cells and other CAF subsets. Further, the tumor tissues of MUC16 whole-body knockout (KPCM) showed dysregulation in the markers of actomyosin assembly and fibroblast differentiation (iCAF and myCAF), indicating that MUC16 has an extra-tumoral role in controlling CAF differentiation. Although we found mesothelium-derivative stro

SUBMITTER: Chirravuri-Venkata R 

PROVIDER: S-EPMC9936860 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature