SMYD3-CDCP1 Axis Drives EMT and CAF Activation in Colorectal Cancer and Is Targetable for Oxaliplatin Sensitization.

ABSTRACT: Background: Colorectal cancer (CRC) mortality is predominantly driven by liver metastasis and poor responsiveness to chemotherapy. The histone methyltransferase SMYD3 has been implicated in oncogenic transcriptional programs; however, its downstream effectors and microenvironmental roles in CRC remain unclear. Methods: We investigated whether SMYD3 regulates the transcription and function of the membrane receptor CDCP1, which mediates Src/PKCδ signaling and promotes invasion and stromal remodeling. A combination of molecular assays, including ChIP-qPCR, Western blotting, and co-culture experiments, was employed to examine the SMYD3-CDCP1 axis and its impact on epithelial-mesenchymal transition (EMT), cancer-associated fibroblast (CAF) activation, and oxaliplatin (OXA) sensiti

SUBMITTER: Zhao L 

PROVIDER: S-EPMC12650379 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature