Melanoma is a highly malignant and is a life‐threatening disease with no effective treatment currently. This study aims to evaluate the significance of TUSC3, an endoplasmic reticulum stress (ERS)‐inducible gene and explore its relationship with AKT/GSK3‐β/β‐catenin signalling pathway in melanoma cell WM451. We investigated TUSC3 expression in melanoma cell by qRT‐PCR, CCK‐8 and clonal formation assays were utilized to evaluate cell proliferation. Wound healing and transwell experiments detected cell migration and invasion. Flow cytometry detected the level of apoptosis. Western blot analysed MMP2, MMP9, p‐AKT, p‐GSK3‐β, β‐catenin and AKT, GSK3‐β, ERS‐related proteins and apoptosis‐related proteins in WM451 cells. The results revealed that TUSC3 was remarkably decreased in melanoma cell lines. Overexpression of TUSC3 significantly inhibits melanoma cell WM451 biological functions and promotes expression of ERS‐related proteins in WM451 cells, increases ERS in WM451 cells by inhibiting AKT/GSK3‐β/β‐catenin pathway. These finding suggest that TUSC3 regulates biological functions of melanoma cells WM451 and increases ERS in melanoma cells WM451 via the inhibition of the AKT/GSK3‐β/β‐catenin signalling pathway.

中文翻译：

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候选肿瘤抑制因子3通过调节AKT /GSK3-β/β-catenin途径抑制黑素瘤细胞WM451的生物学功能并增加其内质网应激。

黑色素瘤是一种高度恶性肿瘤，是威胁生命的疾病，目前尚无有效的治疗方法。这项研究旨在评估内质网应激（ERS）诱导基因TUSC3的意义，并探讨其与黑素瘤细胞WM451中AKT /GSK3-β/β-catenin信号通路的关系。我们通过qRT-PCR，CCK-8和黑色素形成实验评估了黑色素瘤细胞中TUSC3的表达，并利用克隆形成分析来评估细胞增殖。伤口愈合和穿孔实验检测到细胞迁移和侵袭。流式细胞仪检测细胞凋亡水平。Western blot分析了WM451细胞中的MMP2，MMP9，p-AKT，p-GSK3-β，β-catenin和AKT，GSK3-β，ERS相关蛋白和凋亡相关蛋白。结果显示，TUSC3在黑素瘤细胞系中显着降低。TUSC3的过表达显着抑制黑素瘤细胞WM451的生物学功能，并促进WM451细胞中ERS相关蛋白的表达，通过抑制AKT /GSK3-β/β-catenin途径而提高WM451细胞中的ERS。这些发现表明，TUSC3通过抑制AKT /GSK3-β/β-catenin信号通路来调节黑素瘤细胞WM451的生物学功能并增加黑素瘤细胞WM451中的ERS。