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Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation
Zhang,Qingyu1,2; Zhou,Wei3; Yu,Shan1; Ju,Yaojun4; To,Sally Kit Yan5; Wong,Alice Sze Tsai5; Jiao,Yufei6; Poon,Terence Chuen Wai4; Tam,Kin Yip4; Lee,Leo Tsz On1,7
2021-01-07
Source PublicationOncogene
ISSN0950-9232
Volume40Issue:1Pages:97-111
Abstract

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.

DOI10.1038/s41388-020-01516-4
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS SubjectBiochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS IDWOS:000582339900002
PublisherSPRINGERNATURE
Scopus ID2-s2.0-85092785844
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Citation statistics
Cited Times [WOS]:15   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorLee,Leo Tsz On
Affiliation1.Cancer Centre,Faculty of Health Sciences,University of Macau,Taipa,Macao
2.Department of Obstetrics and Gynaecology,Affiliated Hospital of Guangdong Medical University,Zhanjiang,524001,China
3.State Key Laboratory of Natural Medicines,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing,210009,China
4.Proteomics,Metabolomics and Drug Development Core,Faculty of Health Sciences,University of Macau,Taipa,Macao
5.School of Biological Sciences,The University of Hong Kong,Pokfulam Road,Hong Kong
6.Department of Pathology,The Second Affiliated Hospital of Harbin Medical University,Harbin,150001,China
7.Centre of Reproduction,Development,and Aging,Faculty of Health Sciences,University of Macau,Taipa,Macao
First Author AffilicationCancer Centre
Corresponding Author AffilicationCancer Centre;  Faculty of Health Sciences
Recommended Citation
GB/T 7714
Zhang,Qingyu,Zhou,Wei,Yu,Shan,et al. Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation[J]. Oncogene,2021,40(1):97-111.
APA Zhang,Qingyu,Zhou,Wei,Yu,Shan,Ju,Yaojun,To,Sally Kit Yan,Wong,Alice Sze Tsai,Jiao,Yufei,Poon,Terence Chuen Wai,Tam,Kin Yip,&Lee,Leo Tsz On.(2021).Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation.Oncogene,40(1),97-111.
MLA Zhang,Qingyu,et al."Metabolic reprogramming of ovarian cancer involves ACSL1-mediated metastasis stimulation through upregulated protein myristoylation".Oncogene 40.1(2021):97-111.
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