Tumour suppressor candidate 3 inhibits biological function and increases endoplasmic reticulum stress of melanoma cells WM451 by regulating AKT/GSK3-β/β-catenin pathway.

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. SIGNIFICANCE OF THE STUDY: Melanoma is a highly malignant and is a life-threatening disease with no effective treatment currently. Therefore, studying the molecular mechanism of melanoma occurrence and metastasis is essential for the treatment of melanoma. Meanwhile, mounting studies suggest that TUSC3 is considered to be closely associated with the development of various malignancies. TUSC3 regulates proliferation, migration and epithelial-to-mesenchymal transition, but the molecular mechanism of the tumour suppressor effects of TUSC3 on melanoma cells is not well understood. Our study demonstrates that TUSC3 inhibits biological function of melanoma cells and increases ERS in melanoma cells by inhibiting AKT/GSK3-β/β-catenin pathway. And this is expected to be a new target and method for the treatment of melanoma.