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线粒体核糖体蛋白S18-2引发染色体不稳定并转化原代大鼠皮肤成纤维细胞。

Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts.

作者信息

Darekar Suhas D, Mushtaq Muhammad, Gurrapu Sreeharsha, Kovalevska Larysa, Drummond Catherine, Petruchek Maria, Tirinato Luca, Di Fabrizio Enzo, Carbone Ennio, Kashuba Elena

机构信息

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kiev, Ukraine.

出版信息

Oncotarget. 2015 Aug 28;6(25):21016-28. doi: 10.18632/oncotarget.4123.

DOI:10.18632/oncotarget.4123
PMID:26023799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4673247/
Abstract

We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells.Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.

摘要

我们之前已经表明，人类线粒体核糖体蛋白MRPS18-2（S18-2）的过表达导致原代大鼠胚胎成纤维细胞永生化。衍生细胞表达胚胎干细胞标志物，并且在永生化细胞中激活了控制细胞增殖、氧化磷酸化、细胞呼吸和其他氧化还原反应的细胞途径。在此我们报告，在S18-2蛋白过表达后，原代大鼠皮肤成纤维细胞发生了细胞转化。细胞经过了超过300次群体倍增，并且在三个测试克隆中有两个在实验动物中引发了肿瘤。转化细胞表现出不依赖贴壁生长和接触抑制丧失；它们表达上皮标志物，如E-钙黏蛋白和β-连环蛋白。转化细胞表现出端粒酶活性增加、细胞周期紊乱和染色体不稳定。综上所述，我们的数据表明S18-2是一种新鉴定的癌蛋白，可能参与肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/d01cef03b268/oncotarget-06-21016-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/882847daeb03/oncotarget-06-21016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/898271e71ab7/oncotarget-06-21016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/f0a17a7f492e/oncotarget-06-21016-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/fd2a0703dba4/oncotarget-06-21016-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/900fcd732aaf/oncotarget-06-21016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/d01cef03b268/oncotarget-06-21016-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/882847daeb03/oncotarget-06-21016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/898271e71ab7/oncotarget-06-21016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/f0a17a7f492e/oncotarget-06-21016-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/fd2a0703dba4/oncotarget-06-21016-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/900fcd732aaf/oncotarget-06-21016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e77c/4673247/d01cef03b268/oncotarget-06-21016-g006.jpg

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本文引用的文献

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2
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EMBO Rep. 2011 Jul 1;12(7):720-6. doi: 10.1038/embor.2011.88.
3
Evidence for mesenchymal-epithelial transition associated with mouse hepatic stem cell differentiation.
MRPS18-2 蛋白水平与前列腺肿瘤的进展相关，并且它可以诱导癌细胞的 CXCR4 依赖性迁移。
Sci Rep. 2018 Feb 2;8(1):2268. doi: 10.1038/s41598-018-20765-8.
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Expression Levels of the Uridine-Cytidine Kinase Like-1 Protein As a Novel Prognostic Factor for Hepatitis C Virus-Associated Hepatocellular Carcinomas.尿苷-胞苷激酶样1蛋白的表达水平作为丙型肝炎病毒相关肝细胞癌的一种新型预后因素
Acta Naturae. 2017 Jul-Sep;9(3):108-114.
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