ZDHHC5-mediated BRAF palmitoylation activates the MAPK pathway and drives cholangiocarcinoma progression - PubMed
2 hours ago
- #cholangiocarcinoma
- #palmitoylation
- #MAPK pathway
- ZDHHC5 expression and protein palmitoylation are increased in cholangiocarcinoma, promoting tumor growth.
- ZDHHC5 mediates palmitoylation of BRAF at Cys194/195, facilitating its membrane localization and stabilizing the protein.
- This palmitoylation activates the MAPK/ERK signaling pathway, and disruption of ZDHHC5 or BRAF palmitoylation inhibits ERK signaling.
- Cholangiocarcinoma cells with high ZDHHC5 show enhanced MAPK pathway activity and greater sensitivity to MAPK inhibitors.
- The study identifies the ZDHHC5-BRAF-ERK axis as a novel therapeutic target for cholangiocarcinoma.