B3GALT4 modulates tumor progression and autophagy by AKT/mTOR signaling pathway in breast cancer.

BACKGROUND

β-1,3-Galactosyltransferase-4 (B3GALT4), a member of the β-1,3-galactosyltransferase gene family, is essential to the development of many malignancies. However, its biological function in breast cancer is still unknown.

METHOD

Publically accessible datasets, as well as quantitative real-time PCR, western blot, and immunohistochemistry on our patient cohort were used to investigate the expression levels of B3GALT4 in breast cancer. The correlation of B3GALT4 expression with clinical histopathological data and mortality in breast cancer patients was investigated. The effects of B3GALT4 in breast cancer in vitro and in vivo were investigated. RNA-seq, western blot, autophagolysosomes, and the fluorescence intensity of LC3 were used to explore the effects of B3GALT4 on autophagy. Western blot and gene set enrichment analysis (GSEA) were used to identify the AKT/mTOR pathway.

RESULTS

B3GALT4 was significantly overexpressed in breast cancer tissues and was positively correlated with some aspects of clinicopathological status and poor prognosis. B3GALT4 overexpression significantly promoted cell proliferation, migration, and invasion, both in vitro and in vivo. B3GALT4 inhibition suppressed breast cancer cell proliferation, migration, and invasion in vitro. Suppression of B3GALT4 triggered autophagy and hindered the AKT/mTOR signaling pathway.

CONCLUSION

According to the present research, B3GALT4 blocked autophagy via the AKT/mTOR pathway and accelerated the growth of breast cancer. B3GALT4 may be an effective target for patients with breast cancer.