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Abstract：
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 in vitro and in vivo. 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.
摘要：
LRP5是Wnt信号通路的关键受体,在舌鳞状细胞癌（TSCC）中仍未被探索。本研究探讨了LRP5基因敲低对TSCC细胞体外和体内生物学行为的影响。我们的发现表明，LRP5敲低显著增强细胞增殖，迁移,和在CAL27和SCC25细胞系中的侵袭。RNA-seq分析揭示了Akt途径的代偿激活，有119个基因在LRP5敲低后显著上调。MMP1表达升高提示其可能参与TSCC进展。Westernblot分析显示Akt磷酸化增加，上调增殖相关PCNA，LRP5敲低后下调凋亡相关的caspase-3。E-cadherin和β-Catenin的下调，与细胞粘附和侵袭相关的蛋白质，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途径激活对于LRP5敲低诱导的CAL27和SCC25细胞的迁移和增殖至关重要。这些结果突出了LRP5作为TSCC的潜在治疗靶标。同时抑制Wnt和Akt信号传导成为TSCC治疗的有希望的方法。
