Lpcat2, short for lysophosphatidylcholine acyltransferase 2, is an enzyme involved in the biosynthesis of polyunsaturated fatty acid (PUFA)-containing phospholipids [2]. It plays a role in lipid-related processes and is associated with multiple biological pathways. Its functions impact various biological processes such as lipid droplet (LD) production, ferroptosis, and inflammatory responses, making it important in understanding normal physiology and disease [2-10]. Genetic models, like gene knockout mice, can be valuable to study its functions.

In a Lpcat2 knockout (Lpcat2-/-) mouse colon cancer model, Lpcat2-/-mice had more severe lesions. Lpcat2 was found to inhibit colorectal cancer (CRC) progression by inducing ferroptosis. It arrested PRMT1 in the cytoplasm of CRC cells, thus attenuating PRMT1's positive regulatory effect on SLC7A11 promoter, which is a ferroptosis regulator [1]. In pancreatic cancer, loss of Lpcat2 repressed LD accumulation, gemcitabine (GEM) resistance, and cell motility in a xenograft mouse model, indicating its role in chemoresistance [3].

In conclusion, Lpcat2 is essential in regulating lipid-related processes that impact disease development. The use of Lpcat2 knockout mouse models has revealed its role in promoting chemoresistance in colorectal and pancreatic cancers, as well as its inhibitory effect on CRC progression through ferroptosis induction. These findings contribute to understanding the mechanisms of these diseases and may provide 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/