Wang Chengze, Li Yongzheng, Miao Xiaoyan, Wang Ying, Yang Guoli
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006, China.
J Cancer. 2024 Apr 15;15(10):3215-3226. doi: 10.7150/jca.93585. eCollection 2024.
The role of LRP5, a critical receptor in the Wnt signaling pathway, remains unexplored in tongue squamous cell carcinoma (TSCC). This study investigates the impact of LRP5 knockdown on the biological behaviors of TSCC cell lines both and . Our findings indicate that LRP5 knockdown significantly enhances cell proliferation, migration, and invasion in CAL27 and SCC25 cell lines. RNA-seq analysis reveals compensatory activation of the Akt pathway, with 119 genes significantly upregulated post-LRP5 knockdown. Elevated MMP1 expression suggests its potential involvement in TSCC progression. Western blot analysis demonstrates increased Akt phosphorylation, upregulated proliferation-related PCNA, and downregulated apoptosis-related caspase-3 after LRP5 knockdown. Down-regulation of E-cadherin and β-Catenin, proteins associated with cell adhesion and invasion, further elucidates the molecular mechanism underlying increased cell migration and invasion. Our study concludes that compensatory Akt pathway activation is essential for the LRP5 knockdown-induced migration and proliferation of CAL27 and SCC25 cells. These results highlight LRP5 as a potential therapeutic target for TSCC. Simultaneous inhibition of Wnt and Akt signaling emerges as a promising approach for TSCC treatment.
低密度脂蛋白受体相关蛋白5（LRP5）作为Wnt信号通路中的关键受体，其在舌鳞状细胞癌（TSCC）中的作用尚未得到充分研究。本研究调查了LRP5基因敲低对TSCC细胞系生物学行为的影响。我们的研究结果表明，LRP5基因敲低显著增强了CAL27和SCC25细胞系的细胞增殖、迁移和侵袭能力。RNA测序分析显示，Akt信号通路存在代偿性激活，LRP5基因敲低后有119个基因显著上调。基质金属蛋白酶1（MMP1）表达升高表明其可能参与TSCC进展。蛋白质印迹分析表明，LRP5基因敲低后Akt磷酸化增加，增殖相关的增殖细胞核抗原（PCNA）上调，凋亡相关的半胱天冬酶-3（caspase-3）下调。与细胞黏附和侵袭相关的E-钙黏蛋白和β-连环蛋白的下调，进一步阐明了细胞迁移和侵袭增加的分子机制。我们的研究得出结论，代偿性Akt信号通路激活对于LRP5基因敲低诱导的CAL27和SCC25细胞迁移和增殖至关重要。这些结果突出了LRP5作为TSCC潜在治疗靶点的作用。同时抑制Wnt和Akt信号通路有望成为TSCC治疗的有效方法。
