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SHARPIN stabilizes ...
SHARPIN stabilizes estrogen receptor a and promotes breast cancer cell proliferation
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- Zhuang, Ting (author)
- Xinxiang Medical University
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- Yu, Sifan (author)
- Xinxiang Medical University,Peking University
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- Zhang, Lichen (author)
- Xinxiang Medical University
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- Yang, Huijie (author)
- Xinxiang Medical University
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- Li, Xin (author)
- Xinxiang Medical University
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- Hou, Yingxiang (author)
- Xinxiang Medical University
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- Liu, Zhenhua (author)
- Xinxiang Medical University
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- Shi, Yuanyuan (author)
- Xinxiang Medical University
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- Wang, Weilong (author)
- Xinxiang Medical University,The Third Affiliated Hospital of Xinxiang Medical University
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- Yu, Na (author)
- The Third Affiliated Hospital of Xinxiang Medical University,Xinxiang Medical University
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- Li, Anqi (author)
- Xinxiang Medical University
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- Li, Xuefeng (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,University of South China
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- Li, Xiumin (author)
- Xinxiang Medical University,The Third Affiliated Hospital of Xinxiang Medical University
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- Niu, Gang (author)
- Phil Rivers Technology (Beijing) Ltd.,University of Balochistan,LemonData biotech (Shenzhen) Ltd.
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- Xu, Juntao (author)
- LemonData biotech (Shenzhen) Ltd.,University of Balochistan,Phil Rivers Technology (Beijing) Ltd.
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- Hasni, Muhammad Sharif (author)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine,University of Balochistan
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- Mu, Kun (author)
- Shandong University
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- Wang, Hui (author)
- Xinxiang Medical University
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- Zhu, Jian (author)
- Xinxiang Medical University,University of Texas Southwestern Medical Center
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(creator_code:org_t)
- 2017-08-19
- 2017
- English 15 s.
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:44, s. 77137-77151
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http://dx.doi.org/10... (free)
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http://www.oncotarge...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Estrogen receptor a is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. In our study, we identified the novel E3 ubiquitin ligase SHARPIN function to facilitate ERα signaling. SHARPIN is highly expressed in human breast cancer and correlates with ERα protein level by immunohistochemistry. SHARPIN expression level correlates with poor prognosis in ERα positive breast cancer patients. SHARPIN depletion based RNA-sequence data shows that ERα signaling is a potential SHARPIN target. SHARPIN depletion significantly decreases ERα protein level, ERα target genes expression and estrogen response element activity in breast cancer cells, while SHARPIN overexpression could reverse these effects. SHARPIN depletion significantly decreases estrogen stimulated cell proliferation in breast cancer cells, which effect could be further rescued by ERα overexpression. Further mechanistic study reveals that SHARPIN mainly localizes in the cytosol and interacts with ERα both in the cytosol and the nuclear. SHARPIN regulates ERα signaling through protein stability, not through gene expression. SHARPIN stabilizes ERα protein via prohibiting ERα protein poly-ubiquitination. Further study shows that SHARPIN could facilitate the mono-ubiquitinaiton of ERα at K302/303 sites and facilitate ERE luciferase activity. Together, our findings propose a novel ERα modulation mechanism in supporting breast cancer cell growth, in which SHARPIN could be one suitable target for development of novel therapy for ERα positive breast cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- Breast cancer
- ER alpha
- Protein stability
- SHARPIN
- Ubiquitination
Publication and Content Type
- art (subject category)
- ref (subject category)
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Oncotarget
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To the university's database
- By the author/editor
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Zhuang, Ting
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Yu, Sifan
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Zhang, Lichen
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Yang, Huijie
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Li, Xin
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Hou, Yingxiang
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show more...
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Liu, Zhenhua
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Shi, Yuanyuan
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Wang, Weilong
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Yu, Na
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Li, Anqi
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Li, Xuefeng
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Li, Xiumin
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Niu, Gang
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Xu, Juntao
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Hasni, Muhammad ...
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Mu, Kun
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Wang, Hui
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Zhu, Jian
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Oncotarget
- By the university
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Lund University