School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Division of Oral and Maxillofacial Surgery, Department of Dentistry, Taipei Medical University Hospital, Taipei, Taiwan.
J Cell Physiol. 2022 Dec;237(12):4551-4562. doi: 10.1002/jcp.30902. Epub 2022 Oct 19.
Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.
口腔鳞状细胞癌 (OSCC) 是一种极为常见的头颈部癌症，其 5 年生存率较差，尤其是在转移性疾病的情况下。白细胞介素 (IL)-11 据报道可促进转移过程中的细胞生长和上皮间质转化。然而，IL-11 在 OSCC 转移中的分子机制尚不清楚。本研究发现，IL-11 通过 IL-11 受体 alpha 亚基/糖蛋白 130 受体上调 OSCC 中的基质金属蛋白酶 13 (MMP-13) 表达，该受体激活磷脂酰肌醇 3-激酶、Ak 株转化和激活蛋白 1 信号通路，从而增强 MMP-13 诱导的肿瘤转移。TIMER2.0 分析显示 MMP-13 和 IL-11 水平之间呈正相关 (r=0.454)。此外，还观察到 OSCC 组织中 IL-11 表达水平较高与淋巴结转移 (p=0.0154) 和临床疾病分期 (p=0.0337) 之间存在强烈的正相关性。IL-11 敲低抑制了 OSCC 细胞的迁移 (p<0.05)。这些证据表明，IL-11 可作为 OSCC 转移的新分子治疗靶点。
