Targeting myoferlin in ER/Golgi vesicle trafficking reprograms pancreatic cancer-associated fibroblasts

ABSTRACT: Pancreatic cancer (PAAD) cells exploit vesicle trafficking proteins such as myoferlin to fuel tumor aggressiveness, yet the presence and function of myoferlin-dependent vesicles in cancer-associated fibroblasts (CAFs) remain unknown. By combining PAAD whole-tumor and single-cell transcriptomic analyses with immunohistochemistry and 2D/3D in vitro models, we link stromal myoferlin to tumor aggressiveness. We identify CAF-specific functions of myoferlin, as MYOF-depleted CAFs present reduced activity and impaired extracellular matrix (ECM) production. Analysis of intracellular vesicles identifies a TGFß-receptor 1 (TGFBR1) trafficking blockade at the ER/Golgi interface upon myoferlin depletion, leading to altered TGFBR1 activation, impaired signal transduction, loss of ECM production and red

SUBMITTER: Raphaël Peiffer 

PROVIDER: S-SCDT-10_1038-S44318-025-00570-6 | biostudies-other |

REPOSITORIES: biostudies-other