Stk3, also known as Mammalian STE20-like protein kinase 2 (MST2), is a core kinase of the Hippo signaling pathway. The Hippo pathway is evolutionarily conserved and regulates numerous biological processes such as cell growth, fate decision, organ size control, and regeneration [1]. Stk3 controls cell growth, apoptosis, and metastasis via the Hippo and MAPK pathways. It is a key molecule in the Hippo signaling network, with its function being related to various physiological and pathological conditions [2].

Genetic inactivation of Stk3 (along with Stk4) in mouse models increases mitochondrial mass and function in adipose tissues, stabilizes uncoupling protein 1 in beige adipose tissue, and confers resistance to metabolic dysfunction induced by high-fat diet feeding. This shows that Stk3 and Stk4 are key physiological suppressors of mitochondrial capacity in adipose tissues, and their levels are regulated by factors like cold exposure and denervation [3]. In ovarian cancer, the overexpression of Stk3 significantly inhibits cell proliferation, apoptosis, and migration in vitro and tumor growth in vivo, suggesting its role in suppressing ovarian cancer progression [4]. In pancreatic cancer, Stk3 promotes apoptosis and inhibits cell migration, invasion, and proliferation by suppressing the PI3K/AKT/mTOR pathway with the assistance of RASSF1, as demonstrated in nude mouse xenograft experiments [5].

In conclusion, Stk3 plays essential roles in regulating biological processes through its involvement in the Hippo pathway. Mouse models with genetic inactivation or overexpression of Stk3 have revealed its significance in diseases such as obesity-related metabolic disorders, ovarian cancer, and pancreatic cancer. These model-based studies provide valuable insights into the functions of Stk3 and potential therapeutic targets for related diseases.