SCFFBXW7/GSK3 beta-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells

doi:10.1158/0008-5472.CAN-18-4032

	SCFFBXW7/GSK3 beta-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells
	Kuai, Xiaoling 2; Li, Long 1; Chen, Ran 1; Wang, Kangjunjie 1; Chen, Min 1; Cui, Binghai 1; Zhang, Yuxue 1; Li, Junqiang 3; Zhu, Hongwen 4,5; Zhou, Hu 4,5
刊名	CANCER RESEARCH
	2019-09-01
卷号	79 期号:17 页码:4387-4398
ISSN号	0008-5472
DOI	10.1158/0008-5472.CAN-18-4032
通讯作者	Gao, Daming(dgao@sibcb.ac.cn)
英文摘要	Gastric cancer is the third leading cause of cancer-related death worldwide. The regulatory mechanisms underlying gastric cancer cell proliferation are largely unclear. Here, we show that the transcription factor GFI1 is associated with advanced clinical gastric cancer progression and promoted gastric cancer cell proliferation partially through inhibition of gastrokine-2 (GKN2) transcription. GFI1 was a degrading substrate of FBXW7, whose loss was observed in gastric cancer. Mechanistically, GSK3 beta-mediated GFI1 S94/S98 phosphorylation triggered its interaction with FBXW7, resulting in SCFFBXW7-mediated ubiquitination and degradation. A nondegradable GFI1 S94A/S98A mutant was more potent in driving gastric cancer cell proliferation and tumorigenesis than wild-type GFI1. Overall, this study reveals the oncogenic role of GFI1 in gastric cancer and provides mechanistic insights into the tumor suppressor function of FBXW7. Significance: These findings demonstrate the oncogenic role of the transcription factor GFI1 and the tumor suppressive function of FBXW7 in gastric cancer.
资助项目	Ministry of Science and Technology of China[2015CB964502] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19020203] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020364] ; National Natural Science Foundation of China[81790253] ; National Natural Science Foundation of China[91853130]
WOS关键词	FBW7 UBIQUITIN LIGASE ; TUMOR-SUPPRESSOR ; C-MYC ; FBXW7 ; EXPRESSION ; APOPTOSIS ; GROWTH ; STATISTICS ; PROGNOSIS ; GENES
WOS研究方向	Oncology
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000484117800010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288760]
专题	中国科学院上海药物研究所
通讯作者	Gao, Daming
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Syst Biol,CAS Ctr Excellence Mol Cell, State Key Lab Cell Biol,Shanghai Inst Biochem & C, Shanghai, Peoples R China 2.Nantong Univ, Dept Gastroenterol, Affiliated Hosp, Nantong, Jiangsu, Peoples R China 3.OrigiMed Inc, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China 6.Nantong Univ, Dept Clin Biobank, Affiliated Hosp, Nantong, Jiangsu, Peoples R China 7.Univ Chinese Acad Sci, Shanghai Jiao Tong Univ,Sch Med, Key Lab Stem Cell Biol,CAS Ctr Excellence Mol Cel, Inst Hlth Sci,Shanghai Inst Biol Sci,Chinese Acad, Shanghai, Peoples R China 8.Nantong Univ, Dept Gen Surg, Affiliated Hosp, Nantong, Jiangsu, Peoples R China 9.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Kuai, Xiaoling,Li, Long,Chen, Ran,et al. SCFFBXW7/GSK3 beta-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells[J]. CANCER RESEARCH,2019,79(17):4387-4398.
APA	Kuai, Xiaoling.,Li, Long.,Chen, Ran.,Wang, Kangjunjie.,Chen, Min.,...&Gao, Daming.(2019).SCFFBXW7/GSK3 beta-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells.CANCER RESEARCH,79(17),4387-4398.
MLA	Kuai, Xiaoling,et al."SCFFBXW7/GSK3 beta-Mediated GFI1 Degradation Suppresses Proliferation of Gastric Cancer Cells".CANCER RESEARCH 79.17(2019):4387-4398.