Effect of STK3 on proliferation and apoptosis of pancreatic cancer cells via PI3K/AKT/mTOR pathway

Pancreatic cancer, as a malignant tumor with a very poor prognosis, has a high mortality. It is imperative to clarify the mechanism of pancreatic cancer development and find suitable targets for diagnosis and treatment. Serine/threonine kinase 3 (STK3) is one of the core kinases of the Hippo pathway and has the ability to inhibit tumor growth. But the biological function of STK3 in pancreatic cancer remains unknown. Here, we confirmed that STK3 has an impact on the growth, apoptosis, and metastasis of pancreatic cancer cells and investigated the related molecular mechanisms. In our research, we found that STK3 is reduced in pancreatic cancer by RT-qPCR, IHC and IF, its expression level is correlated with the clinicopathological features. CCK-8 assay, colony formation assay and flow cytometry were used to detect the effect of STK3 on the proliferation and apoptosis of pancreatic cancer cells. In addition, the Transwell assay was used to detect the ability of cell migration and invasion. The results showed that STK3 promoted apoptosis and inhibited cell migration, invasion and proliferation pancreatic cancer. Gene set enrichment analysis (GSEA) and western blotting are used to predict and verify the pathways related to STK3. Subsequently, we found that the effect of STK3 on proliferation and apoptosis closely related to the PI3K/AKT/mTOR pathway. Moreover, the assistance of RASSF1 plays a significant role the regulation of PI3K/AKT/mTOR pathway by STK3. The nude mouse xenograft experiment demonstrated the tumor suppressive ability of STK3 in vivo. Collectively, this study found that STK3 regulates pancreatic cancer cell proliferation and apoptosis by suppressing the PI3K/AKT/mTOR pathway with the assistance of RASSF1.

Automated summary

Pancreatic cancer is a highly lethal malignant tumor, and understanding its development mechanisms and finding suitable targets for diagnosis and treatment is crucial. This study demonstrates that STK3 plays a role in the growth, apoptosis, and metastasis of pancreatic cancer cells. STK3 promotes apoptosis and inhibits cell migration, invasion, and proliferation in pancreatic cancer through the suppression of the PI3K/AKT/mTOR pathway with the assistance of RASSF1.