LPCAT3 regulates the proliferation and metastasis of serous ovarian cancer by modulating arachidonic acid

  • Transl Oncol. 2025 Feb:52:102256. doi: 10.1016/j.tranon.2024.102256.
Fang Wen  1 ,  Hongjian Ling  1 ,  Rui Ran  1 ,  Xinya Li  1 ,  Houmei Wang  1 ,  Qianfen Liu  2 ,  Min Li  3 ,  Tinghe Yu  4
Affiliations
  • 1. Laboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
  • 2. Women and Children's Hospital, Chongqing Medical University (Chongqing Health Center for Women and Children), China.
  • 3. Laboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
  • 4. Laboratory of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 39733744 DOI: 10.1016/j.tranon.2024.102256
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: LPCAT3 modulated metabolism of arachidonic acid, thereby regulating Ferroptosis and the survival signaling to determine Cancer growth and metastasis.

Keywords
Arachidonic acid; Ferroptosis; LPCAT3; Lipid metabolism; Ovarian cancer.
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