Stk39-flox Mouse

Stk39, a serine/threonine kinase, is involved in multiple crucial biological functions. It participates in DNA damage response pathways, with ATM kinase phosphorylating Stk39 after DNA damage, enabling it to interact with the Mre11-Rad50-Nbs1 complex, recruit to chromatin, and further phosphorylate H2A.X, promoting homologous recombination repair [1]. It also has a role in several signaling pathways such as the PLK1/ERK, PI3K/AKT, and is associated with various diseases including different types of cancers and hypertension.

In cancer research, knockdown of Stk39 in various cancer cell lines shows inhibitory effects. In hepatocellular carcinoma, its depletion attenuated cell growth, metastasis, arrested the cell cycle in G2/M phase, and promoted apoptosis, with Stk39 positively regulating the ERK signaling pathway [2]. In cholangiocarcinoma, Stk39 knockdown suppressed cell proliferation, migration, and invasion, while overexpression facilitated tumor aggressiveness, and it enhanced the progression by activating the PI3K/AKT signaling pathway [3]. In breast cancer, inhibition of Stk39 via knockdown led to SNAI1 destabilization, impairing the EMT phenotype and decreasing tumor cell migration, invasion, and metastasis [4]. In osteosarcoma, Stk39 down-regulation inhibited cell proliferation and invasion, affecting proteins related to these processes [6]. In pancreatic cancer, downregulation of circ-STK39, which is derived from Stk39, suppressed cancer progression [7]. In renal cell carcinoma, suppressing Stk39 expression significantly suppressed cell proliferation and induced apoptosis, with gene set enrichment analysis identifying it as an important regulator of p53 and p38 signaling pathways [9]. Also, in hepatocellular carcinoma, knockdown of Stk39 suppressed cell proliferation, migration, and invasion by repressing the phosphorylation of mitogen-activated protein kinase p38 [8].

In conclusion, Stk39 plays essential roles in DNA damage repair and is significantly involved in the progression of multiple cancers, as revealed by various loss-of-function experiments. These findings suggest that Stk39 could be a potential therapeutic target for treating cancers. Additionally, its association with hypertension indicates its importance in non-cancerous disease areas as well [5].