Lpcat2, short for lysophosphatidylcholine acyltransferase 2, is an enzyme crucial for phosphatidylcholine synthesis. It is involved in lipid-related metabolic pathways, and its activity impacts processes like lipid peroxidation and ferroptosis [2]. Lpcat2 also plays roles in inflammation regulation by co-localizing with TLR4 and influencing macrophage inflammatory gene expression in response to bacterial ligands [4]. Genetic models, such as knockout mice, are valuable for studying its functions.

In colorectal cancer, Lpcat2 knockout (Lpcat2-/-) mice showed more severe lesions. Lpcat2 inhibits CRC cell proliferation by inducing ferroptosis through the PRMT1/SLC7A11 axis. Lpcat2 arrests PRMT1 in the cytoplasm, attenuating its positive regulation of SLC7A11, a ferroptosis regulator [1]. In pancreatic cancer, loss of Lpcat2 repressed lipid droplet (LD) accumulation, gemcitabine resistance, and cell motility, highlighting its role in chemoresistance [3].

In conclusion, Lpcat2 is essential in lipid metabolism-related biological processes. Model-based research, especially Lpcat2 KO mouse models, has revealed its significant roles in diseases like colorectal and pancreatic cancers, mainly in regulating cell proliferation, chemoresistance, and ferroptosis. Understanding Lpcat2 provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Cao, Nan, Zhang, Fangmei, Yin, Jiang, Lin, Ying, Luo, Liyun. 2024. LPCAT2 inhibits colorectal cancer progression via the PRMT1/SLC7A11 axis. In Oncogene, 43, 1714-1725. doi:10.1038/s41388-024-02996-4. https://pubmed.ncbi.nlm.nih.gov/38605214/

2. Merkel, Melanie, Goebel, Bjarne, Boll, Moritz, Steinhilber, Dieter, Culmsee, Carsten. 2023. Mitochondrial Reactive Oxygen Species Formation Determines ACSL4/LPCAT2-Mediated Ferroptosis. In Antioxidants (Basel, Switzerland), 12, . doi:10.3390/antiox12081590. https://pubmed.ncbi.nlm.nih.gov/37627584/

3. Lin, Yuhe, Zhang, Xin, Wang, Yihui, Yao, Wei. 2024. LPCAT2-mediated lipid droplet production supports pancreatic cancer chemoresistance and cell motility. In International immunopharmacology, 139, 112681. doi:10.1016/j.intimp.2024.112681. https://pubmed.ncbi.nlm.nih.gov/39068758/

4. Abate, W, Alrammah, H, Kiernan, M, Tonks, A J, Jackson, S K. 2020. Lysophosphatidylcholine acyltransferase 2 (LPCAT2) co-localises with TLR4 and regulates macrophage inflammatory gene expression in response to LPS. In Scientific reports, 10, 10355. doi:10.1038/s41598-020-67000-x. https://pubmed.ncbi.nlm.nih.gov/32587324/