Dysregulation of ribosome biogenesis and translational capacity is associated with tumor progression of human breast cancer cells.
Dysregulation of ribosome biogenesis and translational capacity is associated with tumor progression of human breast cancer cells.
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DOI：
10.1371/journal.pone.0007147
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发表时间：
2009-09-25
期刊：
影响因子：
3.7
通讯作者：
Diaz JJ
中科院分区：
文献类型：
--
作者：
Belin S;Beghin A;Solano-Gonzàlez E;Bezin L;Brunet-Manquat S;Textoris J;Prats AC;Mertani HC;Dumontet C;Diaz JJ
蛋白质合成是一个基本的细胞过程，核糖体——特别是通过具有核酶活性的核糖体RNA——是这一过程的主要效应物。核糖体生物发生是一个非常复杂的过程，涉及转录以及许多转录后步骤以产生有功能的核糖体。现在已经充分证明，癌细胞中核糖体的产生增加，并且核糖体生物发生在肿瘤进展中起着至关重要的作用。然而，目前严重缺乏数据来确定在肿瘤进展过程中核糖体生物发生和核糖体组装的整个过程是否发生改变，以及这对癌细胞中观察到的翻译控制失调可能产生什么潜在影响。在体外和体内均表现出增强侵袭性的乳腺癌细胞中，我们分析了核糖体生物发生的主要步骤以及所产生核糖体的翻译能力。我们表明，肿瘤发生能力的增加与核仁形态的改变以及核糖体生物发生和功能的深刻定量和定性改变有关。具体而言，具有增强肿瘤侵袭性的细胞显示45S前体rRNA的合成增加，包含43S前体的替代前体RNA合成途径被激活，并且位于28S rRNA的特定位点的转录后甲基化增强。虽然整体翻译活性没有改变，但在具有增强侵袭性的细胞中，内部核糖体进入位点（IRES）起始的翻译，特别是p53 mRNA的翻译效率较低，并且翻译保真度的控制显著降低。这些结果表明，肿瘤侵袭性的增强可能与核糖体控制的深刻定性改变有关，导致癌细胞中翻译质量控制降低。
Protein synthesis is a fundamental cell process and ribosomes - particularly through the ribosomal RNA that display ribozyme activity - are the main effectors of this process. Ribosome biogenesis is a very complex process involving transcriptional as well as many post-transcriptional steps to produce functional ribosomes. It is now well demonstrated that ribosome production is enhanced in cancer cells and that ribosome biogenesis plays a crucial role in tumor progression. However, at present there is an important lack of data to determine whether the entire process of ribosome biogenesis and ribosome assembly is modified during tumor progression and what could be the potential impact on the dysregulation of translational control that is observed in cancer cells. In breast cancer cells displaying enhanced aggressivity, both in vitro and in vivo, we have analyzed the major steps of ribosome biogenesis and the translational capacity of the resulting ribosome. We show that increased tumorigenicity was associated with modifications of nucleolar morphology and profound quantitative and qualitative alterations in ribosomal biogenesis and function. Specifically cells with enhanced tumor aggressivity displayed increased synthesis of 45S pre-rRNA, with activation of an alternative preRNA synthetic pathway containing a 43S precursor and enhanced post-transcriptional methylation of specifc sites located in the 28S rRNA. While the global translational activity was not modified, IRES-initiated translation, notably that of p53 mRNA, was less efficient and the control of translational fidelity was importantly reduced in cells with increased aggressivity. These results suggest that acquisition of enhanced tumor aggressivity can be associated with profound qualitative alterations in ribosomal control, leading to reduced quality control of translation in cancer cells
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影响因子：
3.7
作者：
Behin, Anne;Honore, Stephane;Dumontet, Charles
通讯作者：
Dumontet, Charles
影响因子：
2.8
作者：
MADJAR, JJ;ARPIN, M;REBOUD, JP
通讯作者：
REBOUD, JP
影响因子：
4.5
作者：
Chaudhuri, Sujan;Vyas, Keyur;Mazumder, Barsanjit
通讯作者：
Mazumder, Barsanjit
影响因子：
64.8
作者：
Barna, Maria;Pusic, Aya;Zollo, Ornella;Costa, Maria;Kondrashov, Nadya;Rego, Eduardo;Rao, Pulivarthi H.;Ruggero, Davide
通讯作者：
Ruggero, Davide
DOI：
10.1007/bf00269998
发表时间：
1979-01-01
期刊：
MOLECULAR AND GENERAL GENETICS
影响因子：
--
作者：
MADJAR, JJ;ARPIN, M;REBOUD, JP
通讯作者：
REBOUD, JP