Implication of RNA-Binding Protein La in Proliferation, Migration and Invasion of Lymph Node-Metastasized Hypopharyngeal SCC Cells

The 5-year survival rate for oral cavity cancer is poorer than for breast, colon or prostate cancer, and has improved only slightly in the last three decades. Hence, new therapeutic strategies are urgently needed. Here we demonstrate by tissue micro array analysis for the first time that RNA-binding protein La is significantly overexpressed in oral squamous cell carcinoma (SCC). Within this study we therefore addressed the question whether siRNA-mediated depletion of the La protein may interfere with known tumor-promoting characteristics of head and neck SCC cells. Our studies demonstrate that the La protein promotes cell proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells. We also reveal that La is required for the expression of β-catenin as well as matrix metalloproteinase type 2 (MMP-2) within these cells. Taken together these data suggest a so far unknown function of the RNA-binding protein La in promoting tumor progression of head and neck SCC.

口腔癌的5年生存率低于乳腺癌、结肠癌及前列腺癌，且近三十年来仅获得小幅改善。因此，临床上亟需开发新型治疗策略。本研究首次借助组织微阵列（tissue micro array）分析证实，RNA结合蛋白La在口腔鳞状细胞癌（oral squamous cell carcinoma, SCC）中存在显著过表达。基于此，本研究旨在探究小干扰RNA（siRNA）介导的La蛋白敲减是否会对头颈部鳞状细胞癌细胞已知的促肿瘤特性产生影响。研究结果显示，La蛋白可促进淋巴结转移型下咽鳞状细胞癌细胞的增殖、迁移与侵袭能力。本研究还揭示，在上述细胞中，La蛋白是β-连环蛋白（β-catenin）以及基质金属蛋白酶2（matrix metalloproteinase type 2, MMP-2）表达所必需的调控因子。综上，本研究表明RNA结合蛋白La在头颈部鳞状细胞癌的肿瘤进展调控中存在此前未被报道的功能。