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ACSL1-Mediated Fatty Acid ß-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer.
Zhou, Ying; Li, Yanyu; Chen, Guanfeng; Guo, Xiaoli; Gao, Xiao; Meng, Jing; Xu, Yinxue; Zhou, Nan; Zhang, Bei; Zhou, Xueyan.
Afiliación
  • Zhou Y; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Li Y; Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 221009 Xuzhou, Jiangsu, China.
  • Chen G; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Guo X; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Gao X; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Meng J; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Xu Y; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Zhou N; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
  • Zhang B; Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, 221009 Xuzhou, Jiangsu, China.
  • Zhou X; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, College of Pharmacy, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China.
Front Biosci (Landmark Ed) ; 29(2): 66, 2024 Feb 06.
Article en En | MEDLINE | ID: mdl-38420815
ABSTRACT

BACKGROUND:

Gynecological malignancies, such as endometrial cancer (EC) and uterine cancer are prevalent. Increased Acyl-CoA synthetase long-chain family member 1 (ACSL1) activity may contribute to aberrant lipid metabolism, which is a potential factor that contributes to the pathogenesis of endometrial cancer. This study aimed to elucidate the potential molecular mechanisms by which ACSL1 is involved in lipid metabolism in endometrial cancer, providing valuable insights for targeted therapeutic strategies.

METHODS:

Xenograft mouse models were used to assess the effect of ACSL1 on the regulation of endometrial cancer progression. ACSL1 protein levels were assessed via immunohistochemistry and immunoblotting analysis. To assess the migratory potential of Ishikawa cells, wound-healing and Transwell invasion assays were performed. Changes in lipids in serum samples from mice with endometrial cancer xenotransplants were examined in an untargeted lipidomic study that combined multivariate statistical methods with liquid chromatography‒mass spectrometry (LC/MS).

RESULTS:

Patient sample and tissue microarray data suggested that higher ACSL1 expression is strongly associated with the malignant progression of EC. Overexpression of ACSL1 enhances fatty acid ß-oxidation and 5'-adenylate triphosphate (ATP) generation in EC cells, promoting cell proliferation and migration. Lipidomic analysis revealed that significant changes were induced by ACSL1, including changes to 28 subclasses of lipids and a total of 24,332 distinct lipids that were detected in both positive and negative ion modes. Moreover, pathway analysis revealed the predominant association of these lipid modifications with the AMPK/CPT1C/ATP pathway and fatty acid ß-oxidation.

CONCLUSIONS:

This study indicates that ACSL1 regulates the AMPK/CPT1C/ATP pathway, which induces fatty acid ß-oxidation, promotes proliferation and migration, and then leads to the malignant progression of EC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Ácidos Grasos Límite: Animals / Female / Humans Idioma: En Revista: Front Biosci (Landmark Ed) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Singapur
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Endometriales / Ácidos Grasos Límite: Animals / Female / Humans Idioma: En Revista: Front Biosci (Landmark Ed) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Singapur