Matrix stiffness induces Ca²⁺-DCLK1-PIP5K1A mechanotransduction as a context-specific amplifier in pancreatic cancer progression and chemotherapy resistance.

ABSTRACT: Alterations in extracellular matrix (ECM) architecture and stiffness are hallmarks of aggressive pancreatic cancer progression. However, the mechanisms by which ECM biomechanical properties regulate malignant biological behavior remain unknown. Here, we reveal that calmodulin-dependent protein kinase doublecortin-like kinase 1 (DCLK1) integrates biomechanical signaling and promotes pancreatic cancer cell progression. DCLK1 expression and activation are selectively induced under conditions of high biomechanical stress mediated through the piezo-type mechanosensitive ion channel component 1 (PIEZO1)/calcium/hippocalcin-like protein 1 (HPCAL1) pathway. Consistently, in solid tumor experiments, DCLK1 overexpression under low stiffness conditions facilitates rapid tumor progression and chemores

SUBMITTER: Zhang H 

PROVIDER: S-EPMC12922331 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature