SIK2, also known as serine/threonine-protein kinase SIK2, is a key regulator involved in multiple biological processes. It plays a significant role in energy metabolism-related pathways, such as glycolysis, gluconeogenesis, lipid synthesis, and fatty acids β-oxidation (FAO) [1]. SIK2 is also associated with cell cycle progression, cellular apoptosis, and is involved in the regulation of actin-dependent host response, among others.

In ovarian cancer, SIK2 enhances the Warburg effect by promoting glycolysis and inhibiting oxidative phosphorylation and gluconeogenesis, and also regulates intracellular lipid metabolism, ultimately promoting cancer cell growth, proliferation, invasion, metastasis, and therapeutic resistance [1]. In uveal melanoma, the loss of the LKB1-SIK2 module drives tumorigenesis, enhancing cell proliferation and survival [2]. In clear cell renal cell carcinoma, FTO-mediated autophagy affects SIK2 mRNA stability, which in turn impacts tumor progression [3]. In breast cancer, SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating the Wnt/β-catenin signaling pathway [4].

In conclusion, SIK2 is a multi-functional regulator in various biological processes and disease conditions. Studies using gene knockout or knockdown models in different cancers have revealed its crucial roles in tumorigenesis, progression, and metabolism. These findings highlight SIK2 as a potential therapeutic target for treating cancers such as ovarian, uveal melanoma, clear cell renal cell, and breast cancer.