THBS2 + cancer-associated fibroblasts promote EMT leading to oxaliplatin resistance via COL8A1-mediated PI3K/AKT activation in colorectal cancer.

ABSTRACT: Cancer-associated fibroblasts (CAFs) exert multiple tumor-promoting functions and are key contributors to drug resistance. The mechanisms by which specific subsets of CAFs facilitate oxaliplatin resistance in colorectal cancer (CRC) have not been fully explored. This study found that THBS2 is positively associated with CAF activation, epithelial-mesenchymal transition (EMT), and chemoresistance at the pan-cancer level. Together with single-cell RNA sequencing and spatial transcriptomics analyses, we identified THBS2 specifically derived from subsets of CAFs, termed THBS2 + CAFs, which could promote oxaliplatin resistance by interacting with malignant cells via the collagen pathway in CRC. Mechanistically, COL8A1 specifically secreted from THBS2 + CAFs directly interacts with the ITGB1 rece

SUBMITTER: Zhou X 

PROVIDER: S-EPMC11681647 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature