SMAD4 Palmitoylation Drives a Metabolic-Transcriptional Circuit to Promote Tumorigenesis and Confers Radiosensitivity in Pancreatic Cancer - PubMed
3 hours ago
- #SMAD4
- #pancreatic cancer
- #palmitoylation
- SMAD4 palmitoylation is identified as a new post-translational modification in pancreatic ductal adenocarcinoma (PDAC).
- Palmitoylation of SMAD4 at cysteine 363 is mediated by ZDHHC22 and reversed by APT2.
- This modification enhances SMAD4 stability, promotes interaction with importins, and amplifies transcriptional output, upregulating FASN.
- A positive feedback loop is established between SMAD4 palmitoylation, FASN, and palmitic acid, driving PDAC tumor growth.
- SMAD4 palmitoylation sensitizes PDAC cells to radiotherapy, revealing a dual role in tumor progression and treatment response.
- Clinically relevant SMAD4 mutants (R361C, R361H) show enhanced palmitoylation, highlighting its pathological relevance.
- The findings suggest SMAD4 palmitoylation as a therapeutic target in pancreatic cancer.