Impa2-KO Mouse

Inositol monophosphatase 2 (IMPA2) is involved in the MI-PI cycle, promoting the production of IP3. This in turn elevates intracellular Ca2+ concentration, activating pathways such as NFAT1-mediated activation of MYC [1]. IMPA2 is thus important in metabolic-oncogenic crosstalk, playing a significant role in cell-related biological processes. Genetic models, like transgenic mice, can be used to study IMPA2's functions.

In basal-like breast cancer (BLBC), knockdown of IMPA2 expression inhibited tumorigenicity and metastasis in vitro and in vivo. IMPA2 expression was upregulated in BLBC due to copy number amplification, hypomethylation, and MYC-mediated activation, forming a positive feedback loop with MYC to enhance BLBC aggressiveness [1]. In cervical cancer, IMPA2 silencing inhibited cell proliferation, migration, and induced apoptosis, with the IMPA2/AIFM2/p53 pathway potentially being a new mechanism for paclitaxel treatment [2,3]. In metastatic clear cell renal cell carcinoma, IMPA2 downregulation enhanced mTORC1 activity and restrained autophagy initiation, suggesting it could be a biomarker for mTOR inhibitor or autophagy inducer use [4].

In conclusion, IMPA2 is crucial in the MI-PI cycle and intracellular Ca2+ regulation. Model-based research, especially knockdown experiments in various cancer cell lines, has revealed its significant roles in promoting cancer cell aggressiveness in BLBC and cervical cancer, and its impact on mTORC1-autophagy axis in metastatic clear cell renal cell carcinoma. These findings highlight IMPA2 as a potential therapeutic target in these cancer types.

References:

1. Lei, Xingyu, Liao, Ruocen, Chen, Xingyu, Dai, Zhijun, Dong, Chenfang. 2023. IMPA2 promotes basal-like breast cancer aggressiveness by a MYC-mediated positive feedback loop. In Cancer letters, 582, 216527. doi:10.1016/j.canlet.2023.216527. https://pubmed.ncbi.nlm.nih.gov/38048842/

2. Xie, Kexin, Liu, Lei, Wang, Min, Lin, Yingrui, Zhu, Xiaolin. . IMPA2 blocks cervical cancer cell apoptosis and induces paclitaxel resistance through p53-mediated AIFM2 regulation. In Acta biochimica et biophysica Sinica, 55, 623-632. doi:10.3724/abbs.2023069. https://pubmed.ncbi.nlm.nih.gov/37140233/

3. Zhang, Kan, Liu, Lei, Wang, Min, Tan, Shan, Luo, Lingli. 2020. A novel function of IMPA2, plays a tumor-promoting role in cervical cancer. In Cell death & disease, 11, 371. doi:10.1038/s41419-020-2507-z. https://pubmed.ncbi.nlm.nih.gov/32409648/

4. Kuei, Chia-Hao, Lin, Hui-Yu, Lee, Hsun-Hua, Chen, Kuan-Chou, Lin, Yuan-Feng. 2020. IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma. In Journal of clinical medicine, 9, . doi:10.3390/jcm9040956. https://pubmed.ncbi.nlm.nih.gov/32235551/