MST1 DOWNREGULATES TAZ TUMOUR SUPPRESSOR PROTEIN IN MULTIPLE MYELOMA AND IS A POTENTIAL THERAPEUTIC TARGET.

We have previously reported that TAZ functions as a tumor suppressor in multiple myeloma. MST1 is a serine-threonine kinase upstream of the Hippo-signaling pathway that functions as a tumor suppressor in many non-haematological malignancies. However, its role in hematological malignancies, including MM is still poorly understood. In this paper, we provide evidence that MST1 expression is higher in MM, and negatively correlates with TAZ expression in both cell lines and patient samples. High MST1 expression was associated with poor clinical outcomes. Genetic or pharmacological inhibition of MST1 leads to increased TAZ expression and cell death. Importantly, MST1 inhibitors sensitizes myeloma cells to frontline antimyeloma agent-lenalidomide and dexamethasone. Taken together, our data reveals a key role for MST1 in MM pathogenesis and provide evidence to explore the therapeutic potential of using MST inhibitors to upregulate TAZ expression in MM to promote response to anticancer agents.