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DOI10.1038/s41467-018-02967-w
SCFFBW7-mediated degradation of Brg1 suppresses gastric cancer metastasis
Huang, Li-Yu1,2,3,4,5; Zhao, Junjie3,6; Chen, Hao6; Wan, Lixin3,7; Inuzuka, Hiroyuki3,8; Guo, Jianping3; Fu, Xuhong1,2; Zhai, Yangyang1,2; Lu, Zhaoning1,2; Wang, Xuefei6; Han, Ze-Guang1,2,4,5; Sun, Yihong6; Wei, Wenyi3
2018-09-03
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2018
卷号9
文章类型Article
语种英语
国家Peoples R China; USA; Japan
英文摘要

Brg1/SMARCA4 serves as the ATPase and the helicase catalytic subunit for the multicomponent SWI/SNF chromatin remodeling complex, which plays a pivotal role in governing chromatin structure and gene transcription. However, the upstream signaling pathways regulating Brg1 protein stability and its physiological contribution to carcinogenesis remain largely elusive. Here we report that Brg1 is a bona fide ubiquitin substrate of SCFFBW7. We reveal that CK1 delta phosphorylates Brg1 at Ser31/Ser35 residues to facilitate the binding of Brg1 to FBW7, leading to ubiquitination-mediated degradation. In keeping with a tumor suppressive role of FBW7 in human gastric cancer, we find an inverse correlation between FBW7 and Brg1 expression in human gastric cancer clinical samples. Mechanistically, we find that stabilization of Brg1 in gastric cancer cells suppresses E-cadherin expression, subsequently promoting gastric cancer metastasis. Hence, this previously unknown FBW7/Brg1 signaling axis provides the molecular basis and the rationale to target Brg1 in FBW7-compromised human gastric cancers.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000443466700009
WOS关键词CELL LUNG-CANCER ; FBW7 UBIQUITIN LIGASE ; MESENCHYMAL TRANSITION ; TUMOR SUPPRESSION ; SWI/SNF COMPLEX ; POOR-PROGNOSIS ; NUCLEOSOME ; EXPRESSION ; MUTATIONS ; PROMOTES
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/203668
专题资源环境科学
作者单位1.Shanghai Jiao Tong Univ, Minist Educ, Key Lab Syst Biomed, 800 Dong Chuan Rd, Shanghai 200240, Peoples R China;
2.Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Syst Biomed, Shanghai Ctr Syst Biomed, 800 Dong Chuan Rd, Shanghai 200240, Peoples R China;
3.Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA;
4.Minist Educ, Shanghai MOST Key Lab Dis & Hlth Genom, Chinese Natl Human Genome Ctr Shanghai, 250 Bi Bo Rd, Shanghai 201203, Peoples R China;
5.Minist Educ, Chinese Natl Human Genome Ctr Shanghai, Key Lab Syst Biomed, 250 Bi Bo Rd, Shanghai 201203, Peoples R China;
6.Fudan Univ, Gen Surg Res Inst, Zhongshan Hosp, Dept Gen Surg, Shanghai 200032, Peoples R China;
7.H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA;
8.Tohoku Univ, Ctr Adv Stem Cell & Regenerat Res, Grad Sch Dent, Sendai, Miyagi 9808575, Japan
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GB/T 7714
Huang, Li-Yu,Zhao, Junjie,Chen, Hao,et al. SCFFBW7-mediated degradation of Brg1 suppresses gastric cancer metastasis[J]. NATURE COMMUNICATIONS,2018,9.
APA Huang, Li-Yu.,Zhao, Junjie.,Chen, Hao.,Wan, Lixin.,Inuzuka, Hiroyuki.,...&Wei, Wenyi.(2018).SCFFBW7-mediated degradation of Brg1 suppresses gastric cancer metastasis.NATURE COMMUNICATIONS,9.
MLA Huang, Li-Yu,et al."SCFFBW7-mediated degradation of Brg1 suppresses gastric cancer metastasis".NATURE COMMUNICATIONS 9(2018).
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