ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer

查看全文 作　　者：Kai [1,2]Li;Jian-lin [3]Wu;Baifu [1,2]Qin;Zongmin [1,3]Fan;Qin [1,2]Tang;Weisi [4]Lu;Haipeng [5]Zhang;Fan [6]Xing;Manqi [1,2]Meng;Shaomin [1,2]Zou;Wenxia [1,2]Wei;Honglei [7]Chen;Jian [7]Cai;Huaiming [7]Wang;Hui [8]Zhang;Jiayue [1,2]Cai;Ling [9]Fang;Xiqing [3]Bian;Chuangqi [10]Chen;Ping [1,2,7]Lan;Bart [11]Ghesquiere;Lekun [1,2,7]Fang;Mong-Hong [1,2]Lee

机构地区：[1]Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Disease,The Sixth Affiliated Hospital of Sun Yat-sen University,510655 Guangzhou,China;[2]Guangdong Research Institute of Gastroenterology,The Sixth Affiliated Hospital of Sun Yat-sen University,510655 Guangzhou,China;[3]State Key Laboratory of Quality Research in Chinese Medicine,Macao Institute for Applied Research in Medicine and Health,Macao University of Science and Technology,Macao,China;[4]State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangzhou,China;[5]Department of Pharmacology,School of Medicine,Jinan University,510632 Guangzhou,China;[6]School of Medicine,Sun Yat-sen University,Guangzhou,China;[7]Department of Colorectal Surgery,The Sixth Affiliated Hospital of Sun Yat-sen University,510655 Guangzhou,China;[8]Zhongshan School of Medicine,Sun Yat-sen University,510080 Guangzhou,China;[9]lnstrumental Analysis&Research Center,Sun Yat-sen University,510080 Guangzhou,China;[10]Department of Colorectal Surgery,The First Affiliated Hospital of Sun Yat-sen University,510000 Guangzhou,China;[11]Metabolomics Core Facility,Center for Cancer Biology,VIB,Leuven,Belgium

出　　处：《Cell Research》索引2020年第30卷第2期,共16页

基　　金：Supported by the National Key R&D Program of China(2018YFC0910303 and 2017YFC1308800);the National Natural Science Foundation of China(81630072,81702749,81773098 and 81602429);the Natural Science Foundation of Guangdong Province(2017A030313706);Guangdong Provincial Science and technology plan(2017A020215199);Pearl River S&T Nova Program of Guangzhou(201806010036),the Science and Technology Planning Project of Shenzhen City(JCYJ20170818162249554);Shenzhen Municipal Government of KQTD20170810160226082,Macao Science and Technology Development Fund(009/2017/A1)and National Key Clinical Discipline.The authors would like to thank Dr.Peter Carmeliet for helpful suggestions on the initial draft of the manuscript. 摘　　要：The Serine-Glycien-One-Carbon(SGOC)pathway is pivotal in multiple anabolic processes.Expression levels of SGOC genes are deregulated under tumoeigenic condltions,suggesting panicipation of oncogenes in deregulating the SGOC biosynthetic pathway.However,the underlying mechanism remains elusive.Here,we identifed that Interleukin enfiarccer-binding factor 3(ILF3)is overexpressed in primary CRC patient specimens and correlates with poor progroosis.ILF3 is critical in regulating the SGOC pathway by directly regulating the mRNA stability of SGOC genes,thereby increasing SGOC genes expression and facilitating tumor growth.Mehhanktic studies showed that the EGF-MIEK-ERK pathway nnediates ILF3 phosphorylation,which hin ders E3 ligase speckle-type POZ protein(SPOP)-mediated poly-ubiquitination and degradation of ILF3.Sign iftca ntly,combination of SGOC inhibitor and the anti-EGFR monoclonal antibody cetuximab can hinder the growth of patient-derived xenografts that sustain high ERK-ILF3 levels.Taken together,deregutation of ILF3 via the EGF-ERK signaling plays an important role in systemic serine metabolic reprogramming and confers a predilection toward CRC development.Our findings indicate that clinical evaluation of SCOC inhibitor is warranted for CRC patients with ILF3 overexpression. 关键词：expression. COLORECTAL INTERLEUKIN

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ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer

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