UM  > 健康科學學院
High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin
Fu A.1; Ma S.1; Wei N.1; Tan B.X.X.1; Tan E.Y.2; Luo K.Q.3
2016
Source PublicationOncotarget
ISSN19492553
Volume7Issue:31Pages:50239-50257
Abstract

Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model. Our study demonstrated that fluid shear stresses triggered apoptosis of breast cancer cells in circulation by elevating the mitochondrial production of the primary free radical, superoxide anion. Cancer cells with high levels of manganese superoxide dismutase (MnSOD) exhibited stronger resistance to shear forceinduced apoptosis and formed more lung metastases in mice. These metastasized cells further displayed higher resistance to chemotherapeutic agent doxorubicin, which also generates superoxide in mitochondria. Specific siRNA-mediated MnSOD knockdown reversed all three phenotypes. Our findings therefore suggest that MnSOD plays an important integrative role in supporting cancer cell survival in circulation, metastasis, and doxorubicin resistance. MnSOD can serve as a new biomarker for identifying metastatic CTCs and a novel therapeutic target for inhibiting metastasis and destroying doxorubicin-resistant breast cancer cells.

KeywordApoptosis Breast Cancer Metastasis Circulating Tumor Cells Doxorubicin Resistance Mnsod
DOI10.18632/oncotarget.10360
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000385422000109
Fulltext Access
Citation statistics
Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Nanyang Technological University
2.Tan Tock Seng Hospital
3.Universidade de Macau
Recommended Citation
GB/T 7714
Fu A.,Ma S.,Wei N.,et al. High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin[J]. Oncotarget,2016,7(31):50239-50257.
APA Fu A.,Ma S.,Wei N.,Tan B.X.X.,Tan E.Y.,&Luo K.Q..(2016).High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin.Oncotarget,7(31),50239-50257.
MLA Fu A.,et al."High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin".Oncotarget 7.31(2016):50239-50257.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Fu A.]'s Articles
[Ma S.]'s Articles
[Wei N.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Fu A.]'s Articles
[Ma S.]'s Articles
[Wei N.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Fu A.]'s Articles
[Ma S.]'s Articles
[Wei N.]'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.