Cancer-associated fibroblasts drive gemcitabine resistance in pancreatic cancer by promoting ferroptosis resistance via the PAX6/PAK3/SLC3A2 axis - PubMed
3 days ago
- #chemoresistance
- #pancreatic-cancer
- #ferroptosis
- Gemcitabine resistance in pancreatic cancer is driven by cancer-associated fibroblasts via the PAX6/PAK3/SLC3A2 axis.
- PAK3 is upregulated in gemcitabine-resistant pancreatic cancer cells and tissues, phosphorylating SLC3A2 to enhance its stability and promote ferroptosis resistance.
- FGF1 secreted by cancer-associated fibroblasts upregulates PAX6, which increases PAK3 transcription, leading to SLC3A2 phosphorylation and stability.
- Phosphorylation of SLC3A2 at Serine 175 prevents its ubiquitination by STUB1, enhancing protein stability and contributing to gemcitabine resistance.
- This study identifies a novel mechanism of gemcitabine resistance and suggests potential therapeutic targets for overcoming drug resistance in pancreatic cancer.