Gsk3b, also known as glycogen synthase kinase 3 beta, is a critical serine/threonine kinase. It is a key repressor of the Wnt/β -catenin signaling pathway [3]. Gsk3b has broad biological importance, being involved in processes such as autophagy, cell proliferation, migration, and metabolism [2,5,8]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In cancer research, Gsk3b has diverse roles. In colorectal cancer, phosphorylation of TRAF6 by Gsk3b triggers TRAF6 degradation, attenuating its inhibitory activity towards autophagy-dependent CTNNB1 signaling, thus promoting metastasis [1]. In lung adenocarcinoma, circ-Gsk3b up-regulates Gsk3b, which suppresses cancer cell proliferation, migration, and stemness by inactivating the Wnt/β-catenin signaling [3]. In breast cancer, miR-132-3p downregulates Gsk3b, enhancing etoposide-induced apoptosis [6]. In cervical cancer, Gsk3b promotes cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition [8]. In posttraumatic osteoarthritis, Gsk3b overexpression alleviates cartilage degradation by promoting DNMT1-mediated hypermethylation of NR4A3 promoter [4]. Also, inhibition of Gsk3b phosphorylation improves glucose and lipid metabolism disorder [5]. In allergic rhinitis, miR-214-3p targets Gsk3b to facilitate M2 macrophage polarization [7].

In conclusion, Gsk3b is a multifunctional kinase involved in numerous biological processes and diseases. Studies using KO/CKO mouse models or other functional assays have revealed its significance in cancer progression, metabolic regulation, and inflammation-related diseases, providing potential therapeutic targets for these conditions.

References:

1. Wu, Hua, Lu, Xing-Xing, Wang, Jing-Ru, Guo, Peng-Da, Li, Jian-Ming. 2019. TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/β-catenin degradation and is targeted for GSK3B/GSK3β-mediated phosphorylation and degradation. In Autophagy, 15, 1506-1522. doi:10.1080/15548627.2019.1586250. https://pubmed.ncbi.nlm.nih.gov/30806153/

2. Ryu, Hye Young, Kim, Leah Eunjung, Jeong, Hyeonjeong, Kim, Eun-Kyoung, Yu, Seong-Woon. 2021. GSK3B induces autophagy by phosphorylating ULK1. In Experimental & molecular medicine, 53, 369-383. doi:10.1038/s12276-021-00570-6. https://pubmed.ncbi.nlm.nih.gov/33654220/

3. Zhu, Ming-Chuang, Zhang, Yan-Hong, Xiong, Peng, Li, Guo-Liang, Zhu, Min. 2022. Circ-GSK3B up-regulates GSK3B to suppress the progression of lung adenocarcinoma. In Cancer gene therapy, 29, 1761-1772. doi:10.1038/s41417-022-00489-8. https://pubmed.ncbi.nlm.nih.gov/35821283/

4. Lv, Zhou, Sun, Deping, Li, Xin, Wu, Gang. 2022. GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1-Mediated Hypermethylation of NR4A3 Promoter. In Disease markers, 2022, 4185489. doi:10.1155/2022/4185489. https://pubmed.ncbi.nlm.nih.gov/35747513/

5. Yan, Ze, Cao, Xiaojuan, Sun, Shouxiang, Sun, Bing, Gao, Jian. 2023. Inhibition of GSK3B phosphorylation improves glucose and lipid metabolism disorder. In Biochimica et biophysica acta. Molecular basis of disease, 1869, 166726. doi:10.1016/j.bbadis.2023.166726. https://pubmed.ncbi.nlm.nih.gov/37146915/

6. Xu, Chengshan, Du, Zhongli, Ren, Simei, Pian, Yaya. . Downregulation of GSK3B by miR-132-3p Enhances Etoposide-Induced Breast Cancer Cell Apoptosis. In Annals of clinical and laboratory science, 51, 285-294. doi:. https://pubmed.ncbi.nlm.nih.gov/34162557/

7. Peng, Ling-Yan, Li, Bi-Bao, Deng, Ke-Bin, Wang, Wen-Guang. 2022. MicroRNA-214-3p facilitates M2 macrophage polarization by targeting GSK3B. In The Kaohsiung journal of medical sciences, 38, 347-356. doi:10.1002/kjm2.12487. https://pubmed.ncbi.nlm.nih.gov/35005835/

8. Zheng, Yanhong, Yang, Yang, Zhu, Weiyan, Liu, Yongzhu, Hu, Qinglan. 2024. GSK3B inhibition reduced cervical cancer cell proliferation and migration by modulating the PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition. In Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 57, e13796. doi:10.1590/1414-431X2024e13796. https://pubmed.ncbi.nlm.nih.gov/39166606/