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Liver kinase B1 (LKB1), a tumour suppressor, participates in many cellular processes, including cell survival, growth, apoptosis, transformation, and metabolism. Upon performing yeast two-hybrid screening, co-immunoprecipitation, and GST pull-down, we identified that BRCA1-associated protein 1 (BAP1), a deubiquitinase, interacts with LKB1. Immunoblotting was performed to examine the effect of BAP1 on the activation of 5′ AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), downstream of LKB1. The relationship between BAP1 deficiency and cancer cell proliferation was examined using cell survival assay and soft agar assay. qRT-PCR and oil red O staining were performed to evaluate lipid synthesis. Our findings reveal that BAP1 deubiquitinates LKB1, inhibits its degradation, and stabilises it, thereby affecting AMPK activation and downstream mTOR activity. BAP1 deficiency may enhance cellular proliferation as well as lipid synthesis. • Tumour suppressor deubiquitinase BAP1 interacts with and deubiquitinates LKB1. • BAP1 regulates the LKB1-AMPK-mTOR signalling pathway. • BAP1 deficiency promotes survival and proliferation of cancer cells via mTOR activation. • BAP1 deficiency enhances lipid synthesis. [ABSTRACT FROM AUTHOR]

MK8722 is a potent and systemic pan-AMPK activator. It is an effective, direct, allosteric activator of AMPK complex in many mammals. This study tried to explore the underlying anti-cancer molecular mechanism of MK8722 in human pancreatic cancer cells (PCCs). The anti-proliferation, invasion and migration functions of MK8722 in human pancreatic cancer analyzed by real time cellular analysis, colony formation assay, cell migration assay, transwell assay and flow cytometery analysis. Moreover, the potential targeted signaling pathway was tested via RNA-seq and pathway enrichment analysis. In the present study, we investigated the anti-PCCs effects of MK8722 on two different human pancreatic cancer cell lines (PANC-1 and Patu8988). The results showed that MK8722 significantly inhibited human tumor cells proliferation and migration/invasion in a dose-dependent manner. Additionally, the influence of MK8722 was examined by analyzing the expression of potential key genes and pathways, which may provide novel insights to the mechanism of MK8722. The inhibition of pancreatic cancer by MK8722 through a number of pathways that inhibit carcinoma proliferation, invasion and migration. The potential effect of MK8722 might be determined by regulating the expression of AL162151, IER2, REPIN1, KRT80 to inhibit cycle arrest and migration. [ABSTRACT FROM AUTHOR]