Wen Fang, Ling Hongjian, Ran Rui, Li Xinya, Wang Houmei, Liu Qianfen, Li Min, Yu Tinghe
Laboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Women and Children's Hospital, Chongqing Medical University (Chongqing Health Center for Women and Children), China.
Transl Oncol. 2025 Feb;52:102256. doi: 10.1016/j.tranon.2024.102256. Epub 2024 Dec 28.
Lysophosphatidylcholine acyltransferase 3 (LPCAT3) promotes ferroptosis through the incorporating polyunsaturated fatty acids into membrane phospholipids, however, its role in serous ovarian cancer remains unclear. Here explored cancer proliferation and metastasis after modulating LPCAP3.
LPCAT3 protein in ovarian cancer tissues was detected using bioinformatic and immunohistoche mical assays. Cell behaviors were observed after up- or down-regulating LPCAT3. Lipid metabolites were determined, and then the pathway enrichment analysis was performed.
The expression level of LPCAT3 in serous ovarian cancer tissues was lower than that in other types of ovarian cancer, and high expression was associated with a longer survival time. Overexpressing LPCAT3 reduced cell proliferation, migration and invasion via enhancing ferroptosis and decreasing the survival signaling; these behaviors were enhanced in LPCAT3-downknocked cells, where a higher abundance of arachidonic acid was observed followed by up-regulation of the downstream survival signaling. In vivo, up-regulation of LPCAT3 decreased tumor growth, but down-regulation enhanced tumor growth and metastasis.
LPCAT3 modulated metabolism of arachidonic acid, thereby regulating ferroptosis and the survival signaling to determine cancer growth and metastasis.
溶血磷脂酰胆碱酰基转移酶3（LPCAT3）通过将多不饱和脂肪酸掺入膜磷脂来促进铁死亡，然而，其在浆液性卵巢癌中的作用仍不清楚。在此研究了调节LPCAP3后对癌症增殖和转移的影响。
使用生物信息学和免疫组织化学方法检测卵巢癌组织中的LPCAT3蛋白。上调或下调LPCAT3后观察细胞行为。测定脂质代谢物，然后进行通路富集分析。
浆液性卵巢癌组织中LPCAT3的表达水平低于其他类型的卵巢癌，高表达与较长的生存时间相关。过表达LPCAT3通过增强铁死亡和减少生存信号来降低细胞增殖、迁移和侵袭；在LPCAT3敲低的细胞中这些行为增强，在这些细胞中观察到更高丰度的花生四烯酸，随后下游生存信号上调。在体内，上调LPCAT3可降低肿瘤生长，但下调则增强肿瘤生长和转移。
LPCAT3调节花生四烯酸代谢，从而调节铁死亡和生存信号，以决定癌症的生长和转移。
