期刊
ONCOGENE
卷 40, 期 1, 页码 97-111出版社
SPRINGERNATURE
DOI: 10.1038/s41388-020-01516-4
关键词
-
资金
- Science and Technology Development Fund, Macau SAR [0016/2020/A1]
- University of Macau [MYRG2019-00075-FHS]
- Hong Kong Research Grant Council [GRF17105919]
Metabolic alterations, particularly in the fatty-acid metabolism, play a key role in promoting cancer cell metastasis, with the protein ACSL1 identified as a crucial regulator in enhancing metastasis through regulating FA metabolism and myristoylation. The study highlights the importance of understanding metabolic reprogramming in cancer progression and the potential for targeting ACSL1 as a therapeutic strategy for inhibiting metastasis.
As a result of the hostile microenvironment, metabolic alterations are required to enable the malignant growth of cancer cells. To understand metabolic reprogramming during metastasis, we conducted shotgun proteomic analysis of highly metastatic (HM) and non-metastatic (NM) ovarian cancer cells. The results suggest that the genes involved in fatty-acid (FA) metabolism are upregulated, with consequent increases of phospholipids with relatively short FA chains (myristic acid, MA) in HM cells. Among the upregulated proteins, ACSL1 expression could convert the lipid profile of NM cells to that similar of HM cells and make them highly aggressive. Importantly, we demonstrated that ACSL1 activates the AMP-activated protein kinase and Src pathways via protein myristoylation and finally enhances FA beta oxidation. Patient samples and tissue microarray data also suggested that omentum metastatic tumours have higher ACSL1 expression than primary tumours and a strong association with poor clinical outcome. Overall, our data reveal that ACSL1 enhances cancer metastasis by regulating FA metabolism and myristoylation.
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