MYO9B deficiency promoted head and neck tumor progression through HIF1α/MYC/STAT2 signaling pathway

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 9; p. 130834
• Main Authors: Gao, Simin, Gao, Xia, Wang, Ning, Xie, Yuping, Tang, Yuedi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2025
• Subjects: c-Myc; Cell Line, Tumor; Cell Movement; Cell Proliferation; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; HIF1α; HNSC; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Male; MYO9B; Myosins - deficiency; Myosins - genetics; Myosins - metabolism; Prognosis; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Signal Transduction; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; STAT2; MYO9B; c-Myc; HIF1α; STAT2; HNSC
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130834

Myosin, a protein family primarily involved in muscle contraction and cell movement, plays critical roles in various biological processes. Increasing evidence suggests its implication in tumor development and progression. However, the underlying mechanism remains poorly understood. Our study aimed to explore the role and molecular mechanism of myosin IXB (MYO9B) in head and neck squamous cell carcinoma (HNSC) development. Utilizing The Cancer Genome Atlas (TCGA) database (n = 24) and analyzing clinical HNSC tissues (n = 24), we investigated the correlation between myosin encoding genes and HNSC progression. Cell proliferation and migration were assessed using CCK8 and Transwell assays to elucidate the tumor suppressive role of MYO9B. Additionally, Western blotting and immunostaining were conducted to evaluate the activation of HIF1α/c-Myc/STAT2 signaling. A 3D Matrigel Primary tumor cell culture model was established to assess the cisplatin resistance of HNSC cells. We found that MYO9B deficiency predicted poor prognosis in HNSC patients. In vitro, inhibiting MYO9B enhanced the proliferative and migratory characteristics of HNSC cell lines. Mechanistically, our study showed that MYO9B deficiency upregulated HIF1α signaling, leading to c-Myc upregulation, which induced stem-like phenotypes in cancer cells and HNSC progression. Furthermore, c-Myc upregulated downstream STAT2 signaling, contributing to cisplatin resistance in HNSC cells. Blocking STAT2 signaling improved cisplatin outcomes in primary MYO9B-high HNSC tissues from patients. Our study highlights the tumor suppressive role of MYO9B through HI1F1α/c-Myc/STAT2 in HNSC, suggesting its potential as a diagnostic indicator and therapeutic target for clinical intervention. •MYO9B deficiency accelerates HNSC progression via the HIF1α/c-Myc/STAT2 axis.•Loss of MYO9B enhances tumor stemness and metabolic reprogramming through HIF1α-driven c-Myc activation.•MYO9B depletion upregulates c-Myc-mediated STAT2 signaling, conferring cisplatin resistance.•Inhibition of STAT2 signaling restores cisplatin sensitivity in MYO9B-deficient HNSC.