Stk16, also known as Krct/PKL12/MPSK1/TSF-1, is a myristoylated and palmitoylated Ser/Thr protein kinase ubiquitously expressed and conserved among eukaryotes. It belongs to the NAK kinase family with an atypical activation loop. Stk16 is membrane-associated, mainly localized to the Golgi, and participates in the TGF-β signaling pathway, TGN protein secretion and sorting, cell cycle, and Golgi assembly regulation [1].

In colorectal cancer, Stk16 phosphorylates c-MYC at serine 452, preventing its degradation via the ubiquitin-proteasome pathway, and thus promoting cancer progression. Genetic or pharmacological inhibition of Stk16 curtails cancer growth and c-MYC expression in vivo, highlighting it as a potential therapeutic target [2]. In lung adenocarcinoma, high Stk16 expression is associated with poor prognosis, and silencing it inhibits cell proliferation and promotes apoptosis via the AKT1 pathway. Exosomes from M1 macrophages can inhibit cell viability and promote apoptosis by targeting Stk16 through the miR-181a-5p/ETS1 axis [3]. In triple-negative breast cancer, STK16 phosphorylates STAT3 at ser-727 residue, conferring JAK2-inhibition resistance. Dual-inhibition of JAK2/STK16 may be a potential treatment strategy [4].

In conclusion, Stk16 plays crucial roles in multiple cellular processes and disease conditions, especially in cancer. Findings from in vivo studies in cancer models suggest that Stk16 could be a key target for therapeutic intervention in colorectal, lung, and triple-negative breast cancers. These insights help us understand the molecular mechanisms underlying cancer development and provide potential directions for developing new cancer treatments.