Nek9-KO Mouse

NEK9, also known as NIMA-related kinase 9, is involved in multiple cellular processes. It plays a role in primary cilia formation, spindle assembly, chromosome alignment, and centrosome separation. In addition, it is associated with pathways like autophagy, IL-6/STAT3, and is important in cell-cycle progression. Genetic models are valuable for studying its functions [1,4,7,8].

In primary cilia formation, NEK9 acts as a selective autophagy adaptor for MYH9/myosin IIA. Mutation in the LC3-interacting region (LIR) of NEK9 in mice impairs in vivo cilia formation in the kidneys, indicating its significance in this process [1]. In cancer, studies show diverse roles. For example, in gastric cancer, NEK9 is a novel effector of IL-6/STAT3, regulating metastasis by targeting ARHGEF2 phosphorylation [2]. In colon cancer, overexpression of the NEK9-EG5 axis is associated with distant metastasis [3]. In breast cancer, decreased Nek9 expression correlates with aggressive behavior and poor prognosis [4]. In pancreatic cancer, USP19 stabilizes NEK9, which then phosphorylates Raptor to inhibit the mTORC1 signaling pathway, leading to autophagic cell death [5]. In gastric cancer, CAF-derived SLIT2 activates NEK9, promoting metastasis [6]. Also, NEK9 is crucial for the proliferation of p53-inactivated cancer cells [8].

In summary, NEK9 is essential for primary cilia formation, cell-cycle regulation, and has significant implications in cancer development and metastasis. Mouse models, especially those with NEK9 mutations, have provided insights into its role in ciliogenesis and cancer-related processes, highlighting its potential as a therapeutic target in these disease areas.