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

ABSTRACT: Pancreatic adenocarcinoma (PAAD) cells exploit vesicle trafficking proteins, such as myoferlin (encoded by MYOF), 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 exhibit reduced activity and impaired extracellular matrix (ECM) production. Analysis of intracellular vesicles shows that myoferlin depletion results in a TGFß-receptor 1 (TGFBR1) trafficking blockade at the ER/Golgi interface upon myoferlin depletion, leading to altered TGFBR1 activation, i

SUBMITTER: Peiffer R 

PROVIDER: S-EPMC12623807 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature