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J Cancer 2024; 15(10):3215-3226. doi:10.7150/jca.93585 This issue Cite

Research Paper

Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling

Chengze Wang*, Yongzheng Li*, Xiaoyan Miao, Ying Wang, Guoli Yang✉

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.
* Chengze Wang And Yongzheng Li contributed equally to this article.

✉ Corresponding author: Guoli Yang, E-mail: guo_li1214edu.cn, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310006, China phone: +86-13600529781.

Citation:
Wang C, Li Y, Miao X, Wang Y, Yang G. Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling. J Cancer 2024; 15(10):3215-3226. doi:10.7150/jca.93585. https://www.jcancer.org/v15p3215.htm
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Abstract

Graphic 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.

Keywords: LRP5, Akt signaling pathway, Tongue squamous cell carcinoma, Invasion, Wnt pathway

Citation styles

APA
Wang, C., Li, Y., Miao, X., Wang, Y., Yang, G. (2024). Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling. Journal of Cancer, 15(10), 3215-3226. https://doi.org/10.7150/jca.93585.

ACS
Wang, C.; Li, Y.; Miao, X.; Wang, Y.; Yang, G. Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling. J. Cancer 2024, 15 (10), 3215-3226. DOI: 10.7150/jca.93585.

NLM
Wang C, Li Y, Miao X, Wang Y, Yang G. Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling. J Cancer 2024; 15(10):3215-3226. doi:10.7150/jca.93585. https://www.jcancer.org/v15p3215.htm

CSE
Wang C, Li Y, Miao X, Wang Y, Yang G. 2024. Knockdown of LRP5 Promotes Proliferation and Invasion of Tongue Squamous Cell Carcinoma through Compensatory Activation of Akt Signaling. J Cancer. 15(10):3215-3226.

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