Matrix stiffness induces Ca2+-DCLK1-PIP5K1A mechanotransduction as a context-specific amplifier in pancreatic cancer progression and chemotherapy resistance - PubMed
6 days ago
- #mechanotransduction
- #pancreatic cancer
- #chemotherapy resistance
- Matrix stiffness in pancreatic cancer induces Ca2+-DCLK1-PIP5K1A mechanotransduction, promoting tumor progression and chemotherapy resistance.
- DCLK1 activation is mediated through the PIEZO1/calcium/HPCAL1 pathway under high biomechanical stress.
- DCLK1 overexpression under low stiffness conditions accelerates tumor progression and chemoresistance, while calcium inhibitors can partially reverse these effects.
- Under high stiffness conditions, DCLK1 knockdown inhibits tumor growth and enhances chemosensitivity but reduces the effect of calcium inhibitors on chemotherapy efficacy.
- DCLK1 interacts with PIP5K1A, inhibiting its threonine phosphorylation and promoting PIP5K1A membrane localization, which activates the PI3K-AKT signaling pathway.
- Targeting the calcium/DCLK1 signaling axis may improve the efficacy of adjuvant therapies in pancreatic cancer.