Myosin-10 promotes angiogenesis and malignant phenotypes in thyroid cancer through functional association with the FGF/FGFR1 signaling axis

Thyroid cancer (TC) is the most prevalent endocrine malignancy globally, with angiogenesis and invasion-driven aggressive progression posing a major clinical challenge. Myosin-10 (MYH10), involved in tumor cell motility and cytoskeletal rearrangement, has unclear functional roles and mechanisms in TC angiogenesis and malignant progression. This study aimed to investigate MYH10’s function and its functional association with the FGF/FGFR1 signaling axis. A stable MYH10 knockdown model was established in human papillary thyroid carcinoma K1 cells; cell proliferation, migration, and invasion were assessed via CCK-8, scratch wound healing, and Transwell assays, with FGF3/FGFR1 detected by Western blot. Human umbilical vein endothelial cells (HUVECs) were treated with conditioned medium from MYH10-knocked-down K1 cells or directly transfected with MYH10 shRNA, followed by VEGFA/CD31 immunofluorescence and tube formation assays. Nude mouse subcutaneous tumor models were established, with HE staining, IHC (VEGFA/CD31/Ki67), WB, single-cell RNA sequencing (scRNA-seq), and CoIP-MS performed. MYH10 knockdown inhibited K1 cell functions, downregulated FGF3/FGFR1, reduced HUVECs’ VEGFA/CD31 expression and tube formation, and suppressed tumor growth/angiogenesis in vivo. CoIP-MS identified FGFR1 as a candidate MYH10-associated protein (1 unique peptide, 0.68% sequence coverage, adjusted P = 0.003; no MYH10-FGF3 binding). scRNA-seq showed altered tumor microenvironment heterogeneity (reduced pro-angiogenic ECs/TAMs, increased quiescent fibroblasts, downregulated angiogenesis genes). These findings establish a functional association between MYH10 and the FGF/FGFR1 axis in K1 cells; however, the low peptide coverage precludes conclusions regarding direct physical binding, and the absence of rescue experiments and additional cell line validation limits definitive pathway dependency claims.