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Research Paper|Volume 15, Issue 21|pp 11860—11874

Lipid reprogramming induced by the NNMT-ABCA1 axis enhanced membrane fluidity to promote endometrial cancer progression

Qirong Wen1, Xiaohui Xie1, Caiyuan Chen3,4, Bolun Wen1, Yaqiong Liu1, Jie Zhou1, Xiaobin Lin2, Han Jin3, Kun Shi1
  • 1Department of Gynecology and Obstetrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
  • 2Department of Breast Surgery and General Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
  • 3Prenatal Diagnosis Center, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
  • 4Department of Obstetrics and Gynecology, Guangzhou Medical University, Guangzhou, China
Received: April 25, 2023Accepted: September 8, 2023Published: October 25, 2023
https://doi.org/10.18632/aging.205142

Copyright: © 2023 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Elucidating the mechanism for the high metastasis capacity of Endometrial cancer (EC) is crucial to improve treatment outcomes of EC. We have recently reported that nicotinamide N-methyltransferase (NNMT) is overexpressed in EC, especially in EC, and predicts poor survival of chemotherapy patients. Here, we aimed to determine the function and mechanism of NNMT on metastasis of EC. Additionally, analysis of public datasets indicated that NNMT is involved in cholesterol metabolism. In vitro, NNMT overexpression promoted migration and invasion of EC by reducing cholesterol levels in the cytoplasm and cell membrane. Mechanistically, NNMT activated ABCA1 expression, leading to cholesterol efflux and membrane fluidity enhancement, thereby promoting EC's epithelial-mesenchymal transition (EMT). In vivo, the metastasis capacity of EC was weakened by targeting NNMT. Our findings suggest a new molecular mechanism involving NNMT in metastasis, poor survival of EC mediated by PP2A and affecting cholesterol metabolism.