MST4 promotes proliferation, invasion, and metastasis of gastric cancer by enhancing autophagy.

BACKGROUND

Mammalian infertile-20-like kinase 4 (MST4) plays major roles in the progression of malignant tumor types, but its function in gastric cancer (GC) remains poorly understood.

OBJECTIVE

To investigate the regulatory mechanism of MST4 in GC.

METHODS

Immunohistochemistry was used to detect MST4 protein in GC tissue. Additionally, the correlation between MST4 expression and the clinicopathological characteristics and prognosis of GC was evaluated. The MST4 expression level in GC cells was measured by western blotting and quantitative real-time polymerase chain reaction. Moreover, the regulatory mechanism of MST4 was investigated in vitro and in vivo.

RESULTS

Overexpression of MST4 was found in GC tissue and cell lines, which correlated to the tumor size, histological type, invasion depth, ulcer, lymph node metastasis, lymphovascular invasion, perineural invasion and TNM stage (all  < 0.01). In terms of MST4 functions in vitro, its upregulation facilitated the proliferation, migration, and invasion of GC cells. Furthermore, MST4 promoted these processes by facilitating autophagy, whereas downregulation of MST4 significantly attenuated these processes. Downregulation of MST4 also attenuated tumor growth in vivo.

CONCLUSION

High expression of MST4 indicates a poor prognosis and promotes GC cell proliferation, invasion, and metastasis by enhancing autophagy.