UM  > 健康科學學院
Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of endoplasmic reticulum stress
Qingyu Zhang1; Shan Yu1; Melody Man Ting Lam2; Terence Chuen Wai Poon2; Litao Sun3; Yufei Jiao4; Alice Sze Tsai Wong5; Leo Tsz On Lee1
2019-03-07
Source PublicationJOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
ISSN1756-9966
Volume38
Abstract

BackgroundAngiotensin II (ANGII) and its receptor (AGTR1) have been proposed as significant contributors to metastasis in multiple cancers. Further, high AGTR1 levels are associated with poor epithelial ovarian cancer (EOC) outcomes. However, the mechanistic basis for these effects is unknown. Recent studies have suggested that ovarian cancer metastasis is highly dependent on the formation of multicellular spheroids (MCS). To understand the associations between the ANGII/AGTR1 pathway and cancer outcomes, we evaluated the effects of ANGII on MCS formation by ovarian cancer cells and used a proteomic approach to analyze the mechanistic basis.MethodsWe used the data from the GENT database and immunohistochemistry staining to assess the AGTR1 expression in epithelial ovarian cancer (EOC) patients and to assess its role in cancer progression. Colony formation assay, 3D culture assay, and transwell assays were used to analyze the effect of ANGII on the MCS formation and cell migration. The signaling pathways of AGTR1 and transactivation of epidermal growth factor receptor (EGFR) transactivation were investigated by the western blotting analysis. Xenograft models were used to determine the role of AGTR1 in ovarian cancer metastasis. ANGII release from ovarian cancer cells and ANGII levels in the EOC ascites fluid were measured by immunoassay. A shotgun proteomic approach was used to explore the detail molecular mechanism. Modulation of lipid desaturation and endoplasmic reticulum stress were verified by the in vitro and in vivo functional assays.ResultsAGTR1 expression was negatively correlated with EOC prognosis. AGTR1activation significantly enhanced the MCS formation and cell migration. ANGII triggered both of the classical AGTR1 pathway and the EGFR transactivation. ANGII administration increased peritoneal metastasis. In addition, ovarian cancer cells secreted ANGII and enhanced cancer metastasis in a positive feedback manner. Based on the proteomic data, lipid desaturation was activated by induction of stearoyl-CoA desaturase-1 (SCD1), which suggests that inhibition of SCD1 may significantly reduce MCS formation by increasing endoplasmic reticulum stress.ConclusionsANGII promotes MCS formation and peritoneal metastasis of EOC cells. AGTR1 activation increases the lipid desaturation via SCD1 upregulation, which ultimately reduces endoplasmic reticulum stress in MCS. This mechanism explained the association between high levels of AGTR1 and poor clinical outcomes in EOC patients.

KeywordAngiotensin Ii Ovarian Cancer Spheroid Formation Lipogenesis Endoplasmic Reticulum Stress
DOI10.1186/s13046-019-1127-x
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000460746100001
PublisherBMC, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Fulltext Access
Citation statistics
Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorLeo Tsz On Lee
Affiliation1.Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Taipa, Macau
2.Proteomics, Metabolomics and Drug Development Core, Faculty of Health Sciences, University of Macau, Taipa, Macau
3.Department of Ultrasound, The Secondary Affiliated Hospital of Harbin Medical University, Harbin, China
4.Department of Pathology, The Secondary Affiliated Hospital of Harbin Medical University, Harbin, China
5.School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Qingyu Zhang,Shan Yu,Melody Man Ting Lam,et al. Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of endoplasmic reticulum stress[J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2019,38.
APA Qingyu Zhang.,Shan Yu.,Melody Man Ting Lam.,Terence Chuen Wai Poon.,Litao Sun.,...&Leo Tsz On Lee.(2019).Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of endoplasmic reticulum stress.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,38.
MLA Qingyu Zhang,et al."Angiotensin II promotes ovarian cancer spheroid formation and metastasis by upregulation of lipid desaturation and suppression of endoplasmic reticulum stress".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 38(2019).
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Qingyu Zhang]'s Articles
[Shan Yu]'s Articles
[Melody Man Ting Lam]'s Articles
Baidu academic
Similar articles in Baidu academic
[Qingyu Zhang]'s Articles
[Shan Yu]'s Articles
[Melody Man Ting Lam]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Qingyu Zhang]'s Articles
[Shan Yu]'s Articles
[Melody Man Ting Lam]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.