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Gene expression of Cancer-associated fibroblasts from orthotopically engrafted murine colon tumors on the single cell level (Sort-Seq)

ABSTRACT: The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and in cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). While ZEB1 in tumor cells regulates metastasis and therapy resistance, its role in CAFs is largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis is accelerated, whereas invasion and metastasis in sporadic cancers is reduced upon fibroblast-specific loss of Zeb1. Single-cell transcriptomics, histological characterization and in vitro modelling reveal a crucial role in CAF polarization, promoting myofibroblastic features by restricting inflammatory activation. Zeb1 deficiency impairs collagen deposition and CAF barrier function but increasesd NFκB-mediated cytokine production, jointly promoting lymphocyte recruitment and immune checkpoint activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE253639 | GEO | 2024/07/02

REPOSITORIES: GEO

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