Pim2, short for proviral integration site for Moloney murine leukemia virus 2, is a serine/threonine protein kinase functioning as an oncogene. It promotes transcriptional activation of genes related to cell survival, proliferation, and cell-cycle progression. Pim2 is involved in multiple signaling pathways such as p38 MAPK/Erk, NF-κB, and Toll-like receptor 2 (TLR2)/myeloid differentiation primary response 88 (MyD88) pathways [1,2,6]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In hepatocellular carcinoma, Pim2 induced by pro-inflammatory macrophages suppresses immunotherapy efficacy. IL1β from IFNγ-polarized tumor macrophages triggers Pim2 expression in cancer cells via p38 MAPK/Erk and NF-κB signaling, and Pim2 + cancer cells resist T-cell cytotoxicity and immunotherapy [1].

In ovarian endometriosis, Pim2 promotes development by enhancing glycolysis and fibrosis, and Pim2 inhibitor SMI-4a can inhibit this process. A Pim2 knockout mouse model was established to demonstrate its role in vivo [3].

In solid tumors, Pim2 promotes cancer progression. The pan-PIM inhibitor JP11646 induces apoptosis by PIM2 protein degradation in vitro and in vivo in mouse xenograft solid cancer models [4].

In endometriosis, Pim2 phosphorylates PFKFB4 to promote anaerobic glycolysis and cell proliferation [5].

In breast cancer, Pim2 phosphorylates USP27X to promote glycolysis and cancer progression [7].

In inflammatory arthritis, conditional knockout of Pim2 in macrophages or using Pim2 inhibitor HJ-PI01 attenuates arthritis development by inhibiting M1 macrophage polarization [8].

In summary, Pim2 is crucial in processes like cell survival, proliferation, and glycolysis regulation. KO/CKO mouse models have revealed its role in diseases such as hepatocellular carcinoma, endometriosis, solid tumors, breast cancer, and inflammatory arthritis, providing insights for potential therapeutic strategies targeting Pim2 in these disease areas.

References:

1. Wang, Jun-Cheng, Chen, Dong-Ping, Lu, Shi-Xun, Chen, Min-Shan, Zhou, Zhong-Guo. . PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma. In Cancer research, 82, 3307-3320. doi:10.1158/0008-5472.CAN-21-3899. https://pubmed.ncbi.nlm.nih.gov/35802648/

2. Wang, Yixin, Xiu, Jing, Ren, Chune, Yu, Zhenhai. 2021. Protein kinase PIM2: A simple PIM family kinase with complex functions in cancer metabolism and therapeutics. In Journal of Cancer, 12, 2570-2581. doi:10.7150/jca.53134. https://pubmed.ncbi.nlm.nih.gov/33854618/

3. Wang, Mengxue, Fan, Ruiqi, Jiang, Junyi, Yu, Zhenhai, Yang, Tingting. 2023. PIM2 Promotes the Development of Ovarian Endometriosis by Enhancing Glycolysis and Fibrosis. In Reproductive sciences (Thousand Oaks, Calif.), 30, 2692-2702. doi:10.1007/s43032-023-01208-w. https://pubmed.ncbi.nlm.nih.gov/37059967/

4. Katsuta, Eriko, Gil-Moore, Malgorzata, Moore, Justine, Takabe, Kazuaki, Opyrchal, Mateusz. 2022. Targeting PIM2 by JP11646 results in significant antitumor effects in solid tumors. In International journal of oncology, 61, . doi:10.3892/ijo.2022.5404. https://pubmed.ncbi.nlm.nih.gov/35920189/

5. Lu, Chao, Qiao, Pengyun, Fu, Ruihai, Ren, Chune, Yu, Zhenhai. 2022. Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis. In Cell death & disease, 13, 790. doi:10.1038/s41419-022-05241-6. https://pubmed.ncbi.nlm.nih.gov/36109523/

6. Ding, Juncai, Yang, Xiufang, Huang, Huijuan, Wang, Bo. 2022. Role of PIM2 in acute lung injury induced by sepsis. In Experimental and therapeutic medicine, 24, 543. doi:10.3892/etm.2022.11480. https://pubmed.ncbi.nlm.nih.gov/35978927/

7. Han, Xue, Ren, Chune, Lu, Chao, Liu, Lan, Yu, Zhenhai. 2024. Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC. In Oncogene, 43, 2493-2503. doi:10.1038/s41388-024-03097-y. https://pubmed.ncbi.nlm.nih.gov/38969771/

8. Xu, Xiaojun, Xu, Peitao, Shen, Guozhen, Shen, Huiyong, Li, Jinteng. 2025. Targeting macrophage polarization by inhibiting Pim2 alleviates inflammatory arthritis via metabolic reprogramming. In Cellular & molecular immunology, 22, 418-436. doi:10.1038/s41423-025-01268-9. https://pubmed.ncbi.nlm.nih.gov/40000906/