Mammalian STE20-like kinase 1 regulates pancreatic cancer cell survival and migration through Mfn2-mediated mitophagy

摘要

Mammalian STE20-like kinase 1 (MST1) plays an important role in pancreatic cancer progression, but its downstream targets are still unknown. In the present study, our results indicated that MST1 expression was significantly downregulated in pancreatic cancer cell lines (PANC-1, BxPC-3 and HPAC) compared with that in the normal ductal epithelial cell line (hTERT-HPNE). Moreover, MST1 overexpression in PANC-1 cells led to increased apoptosis as determined by MTT and TUNEL assays and inhibited cellular migration. Mechanistically, upregulation of MST1 expression caused mitochondrial dysfunction, decreased ATP production, and activation of the mitochondrial-dependent apoptotic pathway via inhibition of mitofusin 2 (Mfn2)-mediated mitophagy, which ultimately resulted in increased cellular apoptosis and decreased cellular migration. Collectively, the present study demonstrated that MST1 may regulate pancreatic cancer PANC-1 cell survival, invasion and migration through Mfn2-mediated mitophagy, laying the foundation for the exploration of novel therapeutic targets for pancreatic cancer.