Department of Otolaryngology-Head and Neck Surgery, Wuhan No.1 Hospital, Wuhan, People's Republic of China.
Department of Otolaryngology-Head and Neck Surgery, Shiyan Hospital of Integrated Traditional and Western Medicine, Shiyan, People's Republic of China.
Mol Genet Genomics. 2022 Nov;297(6):1529-1536. doi: 10.1007/s00438-022-01934-x. Epub 2022 Aug 11.
Laryngeal Squamous Cell Carcinoma (LSCC) is one of the most common malignancy in Head and neck cancer for which the mechanism underlying its metastasis is poorly understood. Myosin X, a molecular motor in cells has been demonstrated to play an important role in cell migration. However, whether Myosin X is involved in the metastasis of LSCC remains unclear. To investigate the expression of Myosin X and its implication in the metastasis of LSCC, we recruited 30 patients with LSCC and 6 patients with vocal cord polyp range from October 2016 to October 2018. Tissue samples were obtained during surgery and the expression of Myosin X, Cortactin, MMP2, MMP9, E-cadherin, and β-catenin in tissue samples were evaluated by RT-PCR, Western blot, immunohistochemistry or ELISA. Patients with LSCC were further followed-up 2 year after surgery for metastasis analysis. We found that the level of Myosin X, Cortactin, MMP2, and MMP9 was much higher in poorly differentiated LSCC compared to that in moderately and highly LSCC, as well as the control tissues. In contrast, the expression of epithelial-mesenchymal transition related marker, E-cadherin, and β-catenin, were much lower in poorly differentiated LSCC tissues compared to that in moderately and highly differentiated LSCC tissues, as well as the control tissues. Moreover, the expression of Myosin X was positively correlated with Cortactin, MMP2, and MMP9 levels. Increased expression of Myosin X in LSCC tissues was related to higher risk of metastasis. In conclusion, our findings showed that. Myosin X augments the expression of Cortactin, MMP2 and MMP9, which could upregulate the cell migration and the matrix degradation, and consequently reduce the expression of E-cadherin and β-catenin, thereby activating epithelial-mesenchymal transformation and promoting the metastasis of LSCC. Targeting Myosin X may have potential therapeutic effect in the metastasis of LSCC.
喉鳞状细胞癌 (LSCC) 是头颈部癌症中最常见的恶性肿瘤之一,其转移的机制尚不清楚。肌球蛋白 X 是细胞中的一种分子马达,已被证明在细胞迁移中发挥重要作用。然而,肌球蛋白 X 是否参与 LSCC 的转移尚不清楚。为了研究肌球蛋白 X 的表达及其在 LSCC 转移中的作用,我们招募了 2016 年 10 月至 2018 年 10 月期间 30 例 LSCC 患者和 6 例声带息肉患者。在手术期间获得组织样本,并通过 RT-PCR、Western blot、免疫组织化学或 ELISA 评估组织样本中肌球蛋白 X、Cortactin、MMP2、MMP9、E-钙粘蛋白和 β-连环蛋白的表达。LSCC 患者在手术后进一步随访 2 年以进行转移分析。我们发现,与中、高分化 LSCC 组织以及对照组织相比,低分化 LSCC 中肌球蛋白 X、Cortactin、MMP2 和 MMP9 的水平明显更高。相反,低分化 LSCC 组织中上皮-间充质转化相关标志物 E-钙粘蛋白和 β-连环蛋白的表达明显低于中、高分化 LSCC 组织以及对照组织。此外,肌球蛋白 X 的表达与 Cortactin、MMP2 和 MMP9 水平呈正相关。LSCC 组织中肌球蛋白 X 的高表达与转移风险增加有关。总之,我们的研究结果表明,肌球蛋白 X 增强了 Cortactin、MMP2 和 MMP9 的表达,从而增强了细胞迁移和基质降解,进而降低了 E-钙粘蛋白和 β-连环蛋白的表达,从而激活上皮-间充质转化,促进 LSCC 的转移。靶向肌球蛋白 X 可能对头颈部癌症的转移具有潜在的治疗效果。