Lpcat1-KO Mouse

Lpcat1, or lysophosphatidylcholine acyltransferase 1, is a key enzyme in lipid remodeling, converting lysophosphatidylcholine into phosphatidylcholine. It is involved in the Lands cycle, which actively regulates the fatty acyl chain composition of phospholipids, thus determining the biophysical properties of biological membranes [5]. Lpcat1 is crucial for proper lung function as it participates in pulmonary surfactant biosynthesis [5].

Lpcat1 has been implicated in multiple diseases. In cancer, knockdown of Lpcat1 in various cancer cell lines and in vivo models shows significant impacts. In esophageal squamous cell carcinoma (ESCC), Lpcat1 knockdown inhibited cholesterol synthesis, cell proliferation, invasion, migration, and xenograft tumor growth [1]. In lung adenocarcinoma, shRNA-mediated depletion of Lpcat1 abrogated cell proliferation, migration, and invasion in vitro and arrested tumor growth and brain metastases in vivo [2]. In hepatocellular carcinoma (HCC), Lpcat1-knockout hampered cellular proliferation, migration, and metastasis in cell lines [6]. In melanoma, Lpcat1 knockdown induced cell cycle arrest at the G1/S transition and promoted cell death [4]. In cutaneous squamous cell carcinoma (cSCC), loss-of-function experiments demonstrated that Lpcat1 facilitated cell proliferation, protected cells against apoptosis, accelerated epithelial-mesenchymal transition, and enhanced cell metastasis [7]. In psoriasis, Lpcat1 inhibition attenuated epidermal hyperplasia and relieved skin inflammation in imiquimod-treated mice [3].

In conclusion, Lpcat1 is essential for lipid remodeling and pulmonary surfactant biosynthesis. Its role in various diseases, especially cancer, has been revealed through loss-of-function experiments in cell lines and in vivo models. These studies suggest that targeting Lpcat1 could be a potential therapeutic strategy for treating cancer, psoriasis, and other related diseases.

References:

1. Tao, Mingyue, Luo, Jing, Gu, Tong, Luo, Chao, Wang, Qilong. 2021. LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma. In Cell death & disease, 12, 845. doi:10.1038/s41419-021-04132-6. https://pubmed.ncbi.nlm.nih.gov/34518524/

2. Wei, Chunhua, Dong, Xiaomin, Lu, Hui, Wu, Gang, Dong, Xiaorong. 2019. LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway. In Journal of experimental & clinical cancer research : CR, 38, 95. doi:10.1186/s13046-019-1092-4. https://pubmed.ncbi.nlm.nih.gov/30791942/

3. Huang, Yingjian, Wang, Yuqian, Zhen, Yunyue, Yan, Jianjun, Sun, Qing. 2024. LPCAT1 Facilitates Keratinocyte Hyperproliferation and Skin Inflammation in Psoriasis by Regulating GLUT3. In The Journal of investigative dermatology, 144, 1479-1490.e14. doi:10.1016/j.jid.2024.01.004. https://pubmed.ncbi.nlm.nih.gov/38246582/

4. Wang, Yuqian, Huang, Yingjian, Wang, Yan, Tuo, Huihui, Zheng, Yan. 2024. LPCAT1 promotes melanoma cell proliferation via Akt signaling. In Oncology reports, 51, . doi:10.3892/or.2024.8726. https://pubmed.ncbi.nlm.nih.gov/38551165/

5. Wang, Bo, Tontonoz, Peter. 2018. Phospholipid Remodeling in Physiology and Disease. In Annual review of physiology, 81, 165-188. doi:10.1146/annurev-physiol-020518-114444. https://pubmed.ncbi.nlm.nih.gov/30379616/

6. He, Rong-Quan, Li, Jian-Di, Du, Xiu-Fang, Yang, Hong, Chen, Gang. 2021. LPCAT1 overexpression promotes the progression of hepatocellular carcinoma. In Cancer cell international, 21, 442. doi:10.1186/s12935-021-02130-4. https://pubmed.ncbi.nlm.nih.gov/34419067/

7. Huang, Yingjian, Wang, Yuqian, Wang, Yan, Bilal, Muhammad Ahsan, Zheng, Yan. 2021. LPCAT1 Promotes Cutaneous Squamous Cell Carcinoma via EGFR-Mediated Protein Kinase B/p38MAPK Signaling Pathways. In The Journal of investigative dermatology, 142, 303-313.e9. doi:10.1016/j.jid.2021.07.163. https://pubmed.ncbi.nlm.nih.gov/34358528/