HTR7 promotes laryngeal cancer growth through PI3K/AKT pathway activation

Abstract

Background: Laryngeal cancer is a common malignancy of the head and neck, it's important to find novel targets for its therapy. The 5-hydroxytryptamine receptor 7 (HTR7) belongs to the G protein-coupled receptors (GPCRs) family which are easily druggable in diseases; however, its role in laryngeal cancer remains unknown. Methods: Colony formation assay, Soft agar growth assay, BrdU incorporation assay and MTT assay were used to analyze the effect of HTR7 on laryngeal cancer cell proliferation. Xenograft tumors in nude mice was used to analyze the effect of HTR7 on laryngeal cancer growth. Luciferase reporter assay was used to analyze the effect of HTR7 on phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT) pathway activity. Results: We found that HTR7 was significantly upregulated in laryngeal cancer tissues and cells, and patients with high HTR7 expression had shorter survival time than those with low HTR7 expression. Univariate and multivariate Cox regression models showed that HTR7 was an independent predictive factor for the prognosis of patients with laryngeal cancer. Cell proliferation assays and an animal model showed that HTR7 overexpression promoted laryngeal cancer proliferation and growth, while HTR7 knockdown inhibited laryngeal cancer proliferation and growth. Further analysis showed HTR7 activated the PI3K/AKT pathway, characterized by increased phosphorylation of AKT, luciferase reporter activity of forkhead box O (FOXO) factors, and target expression. Inhibition of the PI3K/AKT pathway in HTR7-overexpressing cells suppressed proliferation and growth, suggesting that HTR7 promotes laryngeal cancer proliferation and growth by activating the PI3K/AKT pathway. Conclusions: HTR7 is not only a target for laryngeal cancer therapy but also a prognostic factor for the prognosis of patients with laryngeal cancer.