Myoferlin

Myoferlin (MYOF) is a ferlin-family membrane protein that supports membrane integrity, membrane fusion, endocytosis, and receptor trafficking in non-muscle cells^[1]. Mechanistically, myoferlin stabilizes VEGFR-2 at the endothelial cell surface and enables VEGF-induced proliferation, migration, nitric oxide release, and vascular permeability^[1]. In tumor models, myoferlin also chaperones activated STAT3 to the nucleus during IL-6 signaling, supporting tumor cell migration, tumorsphere formation, cancer stem-cell enrichment, tumor growth, and metastasis^[2]. This vesicle- and receptor-centered function connects myoferlin to tumor angiogenesis, because myoferlin silencing in pancreatic cancer cells impairs VEGFA exocytosis, reduces functional blood vessels, and decreases tumor volume^[3]. In carcinoma models, myoferlin-dependent membrane repair and signaling sustain cancer-cell proliferation and tumor burden^[4]. Compared with the related isoform dysferlin, myoferlin shows distinct epithelial relevance, because myoferlin siRNA, but not dysferlin siRNA, causes cell rounding, adhesion loss, decreased ZO-1, and apoptotic marker increase in airway epithelial cells^[5]. For experimental inhibition, WJ460 directly targets myoferlin and reduces breast-cancer extravasation, while YQ456 binds myoferlin, disrupts Rab-protein interactions, and attenuates colorectal-cancer invasion and progression^[6][7].