[1]董佳杰,党燕梅,张 驰,等.SMURF2在前列腺癌细胞中调节STAT1的泛素化并促进EMT[J].南京师大学报(自然科学版),2021,44(02):62-68.[doi:10.3969/j.issn.1001-4616.2021.02.010]
 Dong Jiajie,Dang Yanmei,Zhang Chi,et al.SMURF2 Regulates STAT1 Ubiquitination and PromotesEMT in Prostate Cancer Cells[J].Journal of Nanjing Normal University(Natural Science Edition),2021,44(02):62-68.[doi:10.3969/j.issn.1001-4616.2021.02.010]
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SMURF2在前列腺癌细胞中调节STAT1的泛素化并促进EMT()
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《南京师大学报(自然科学版)》[ISSN:1001-4616/CN:32-1239/N]

卷:
第44卷
期数:
2021年02期
页码:
62-68
栏目:
·生物学·
出版日期:
2021-06-30

文章信息/Info

Title:
SMURF2 Regulates STAT1 Ubiquitination and PromotesEMT in Prostate Cancer Cells
文章编号:
1001-4616(2021)02-0062-07
作者:
董佳杰党燕梅张 驰蒋 顺刘 平卢 山
南京师范大学生命科学学院,生物化学与生物制品研究所,江苏 南京 210023
Author(s):
Dong JiajieDang YanmeiZhang ChiJiang ShunLiu PingLu Shan
School of Life Sciences,Nanjing Normal University,Institute of Biochemistry and Biological Products,Nanjing 210023,China
关键词:
前列腺癌SMURF2STAT1EMT
Keywords:
prostate cancerSMURF2STAT1EMT
分类号:
Q291
DOI:
10.3969/j.issn.1001-4616.2021.02.010
文献标志码:
A
摘要:
SMURF2(smad ubiquitination regulatory factor 2)属于HECT(homologous to E6AP C terminus)家族E3泛素连接酶,有研究报道SMURF2在不同类型癌症中发挥促癌或抑癌作用. 本研究探讨了SMURF2在前列腺(癌)细胞中调节STAT1(signal transducers and activators of transcription 1)蛋白的分子机制. 首先通过数据库分析SMURF2在正常组织与肿瘤组织间的表达差异,然后选取前列腺正常细胞和多种前列腺癌细胞为实验材料,通过RT-PCR,Western blotting实验检测SMURF2在前列腺(癌)细胞中的表达水平,发现相对于前列腺正常细胞,SMURF2在前列腺癌细胞中表达更高. 再通过Co-IP,免疫荧光和泛素化检测实验观察SMURF2对STAT1蛋白泛素化水平的影响,发现SMURF2可以增加STAT1蛋白的泛素化水平,并进一步促进前列腺癌细胞发生EMT(epithelial mesenchymal transformation).
Abstract:
SMURF2(smad ubiquitination regulatory factor 2)is a HECT(homologous to E6AP C terminus)family E3 ubiquitin ligase. Studies have shown that SMURF2 plays a role in promoting or suppressing cancer progression in different types of cancer. This study explored the molecular mechanism of SMURF2 regulating STAT1(signal transducers and activators of transcription 1)protein in prostate(cancer)cells. The database was firstly used to analyze the expression level of SMURF2 in different normal tissues and tumor tissues. Normal prostate cells and various prostate cancer cells were selected as experimental materials. The expression level of SMURF2 in prostate(cancer)cells was detected by RT-PCR and Western blotting assays,which found that the expression level of SMURF2 was higher in prostate cancer cells than normal prostate cells. Then the Co-IP,immunofluorescence and ubiquitination testing experiments were used to explore the effects on SMURF2 on the ubiquitination of STAT1 protein level,which found that SMURF2 can increase the ubiquitination level of STAT1 protein and further promote EMT(epithelial mesenchymal transformation)in prostate cancer cells.

参考文献/References:

[1] BRAY F,FERLAY J,SOERJOMATARAM I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. A cancer journal for clinicians,2018,68(6):394-424.
[2]CULP M B,SOERJOMATARAM I,EFSTATHIOU J A,et al. Recent global patterns in prostate cancer incidence and mortality rates[J]. European urology,2020,77(1):38-52.
[3]RUETALO N,ANDERS S,STOLLMAIER C,et al. The WW1 domain enhances autoinhibition in smurf ubiquitin ligases[J]. Journal of molecular biology,2019,431(24):4834-4847.
[4]SCHEFFNER M,KUMAR S. Mammalian HECT ubiquitin-protein ligases:biological and pathophysiological aspects[J]. Biochimica et biophysica acta,2014,1843(1):61-74.
[5]ZOU X,LEVY C G,BLANK M. Molecular functions of NEDD4 E3 ubiquitin ligases in cancer[J]. Biochimica et biophysica acta,2015,1856(1):91-106.
[6]DAVID D,NAIR S A,PILLAI M R. Smurf E3 ubiquitin ligases at the cross roads of oncogenesis and tumor suppression[J]. Biochimica et biophysica acta,2013,1835(1):119-128.
[7]KLUPP F,GIESE C,HALAMA N,et al. E3 ubiquitin ligase Smurf2:a prognostic factor in microsatellite stable colorectal cancer[J]. Cancer management and research,2019,11:1795-1803.
[8]TOMAS A,FUTTER C E,EDEN E R. EGF receptor trafficking:consequences for signaling and cancer[J]. Trends in cell biology,2014,24(1):26-34.
[9]DAVID D,JAGADEESHAN S,HARIHARAN R,et al. Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner[J]. Cell division,2014,9:2.
[10]DAVID D,SURENDRAN A,THULASEEDHARAN J V,et al. Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2,and its role in breast cancer progression[J]. BMC cancer,2018,18(1):284.
[11]BLANK M,TANG Y,YAMASHITA M,et al. A tumor suppressor function of Smurf2 associated with controlling chromatin landscape andgenome stability through RNF20[J]. Nature medicine,2012,18(2):227-234.
[12]RAMKUMAR C,KONG Y,CUI H,et al. Smurf2 regulates the senescence response and suppresses tumorigenesis in mice[J]. Cancer research,2012,72(11):2714-2719.
[13]EMANUELLI A,MANIKOTH A D,KOGANTI P,et al. Altered expression and localization of tumor suppressive E3 ubiquitin ligase SMURF2 in human prostate and breast cancer[J]. Cancers(Basel),2019,11(4):556.
[14]WANG Z,WANG J,LI X,et al. Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1,Smurf1 and Smurf2[J]. International journal of oncology,2014,45(4):1469-1478.
[15]HELLWINKEL O J,ASONG L E,ROGMANN J P,et al. Transcription alterations of members of the ubiquitin-proteasome network in prostate carcinoma[J]. Prostate cancer and prostatic diseases,2011,14(1):38-45.
[16]TU Y,CHEN C,PAN J,et al. The ubiquitin proteasome pathway(UPP)in the regulation of cell cycle control and DNA damage repair and its implication in tumorigenesis[J]. International journal of experimental pathology,2012,5(8):726-738.
[17]JANG H H. Regulation of protein degradation by proteasomes in cancer[J]. Journal of cancer prevention,2018,23(4):153-161.
[18]HE M,ZHOU Z,SHAN A A,et al. The emerging role of deubiquitinating enzymes in genomic integrity,diseases,and therapeutics[J]. Cell bioscience,2016,6:62.
[19]KACHROO P,LEE M H,ZHANG L,et al. IL-27 inhibits epithelial-mesenchymal transition and angiogenic factor production in a STAT1-dominant pathway in human non-small cell lung cancer[J]. Journal of experimental & clinical cancer research:CR,2013,32(1):97.
[20]PAN C M,WANG M L,CHIOU S H,et al. Oncostatin M suppresses metastasis of lung adenocarcinoma by inhibiting SLUG expression through coordination of STATs and PIASs signalings[J]. Oncotarget,2016,7(37):60395-60406.

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备注/Memo

备注/Memo:
收稿日期:2020-05-03.
基金项目:国家自然科学基金项目(81272850、81472415).
通讯作者:卢山,博士,教授,研究方向:前列腺肿瘤侵袭转移的分子机制及调控. E-mail:lu_shan@hotmail.com
更新日期/Last Update: 2021-06-30