Ribosome Biogenesis Alterations in Colorectal Cancer
Many studies have focused on understanding the regulation and functions of aberrant protein synthesis in colorectal cancer (CRC), leaving the ribosome, its main effector, relatively underappreciated in CRC. The production of functional ribosomes is initiated in the nucleolus, requires coordinated ri...
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doaj-637ec8dbee47453f898654b7f88bb0502020-11-25T03:52:36ZengMDPI AGCells2073-44092020-10-0192361236110.3390/cells9112361Ribosome Biogenesis Alterations in Colorectal CancerSophie Nait Slimane0Virginie Marcel1Tanguy Fenouil2Frédéric Catez3Jean-Christophe Saurin4Philippe Bouvet5Jean-Jacques Diaz6Hichem C. Mertani7Cancer Initiation and Tumor Cell Identity, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1052, CNRS UMR5286 Centre Léon Bérard, 69008 Lyon, FranceCancer Initiation and Tumor Cell Identity, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1052, CNRS UMR5286 Centre Léon Bérard, 69008 Lyon, FranceInstitute of Pathology EST, Hospices Civils de Lyon, Site-Est Groupement Hospitalier- Est, 69677 Bron, FranceCancer Initiation and Tumor Cell Identity, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1052, CNRS UMR5286 Centre Léon Bérard, 69008 Lyon, FranceGastroenterology and Genetic Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69008 Lyon, FranceCancer Initiation and Tumor Cell Identity, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1052, CNRS UMR5286 Centre Léon Bérard, 69008 Lyon, FranceCancer Initiation and Tumor Cell Identity, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1052, CNRS UMR5286 Centre Léon Bérard, 69008 Lyon, FranceCancer Initiation and Tumor Cell Identity, Cancer Research Center of Lyon, Université de Lyon, Université Claude Bernard Lyon 1, Inserm U1052, CNRS UMR5286 Centre Léon Bérard, 69008 Lyon, FranceMany studies have focused on understanding the regulation and functions of aberrant protein synthesis in colorectal cancer (CRC), leaving the ribosome, its main effector, relatively underappreciated in CRC. The production of functional ribosomes is initiated in the nucleolus, requires coordinated ribosomal RNA (rRNA) processing and ribosomal protein (RP) assembly, and is frequently hyperactivated to support the needs in protein synthesis essential to withstand unremitting cancer cell growth. This elevated ribosome production in cancer cells includes a strong alteration of ribosome biogenesis homeostasis that represents one of the hallmarks of cancer cells. None of the ribosome production steps escape this cancer-specific dysregulation. This review summarizes the early and late steps of ribosome biogenesis dysregulations described in CRC cell lines, intestinal organoids, CRC stem cells and mouse models, and their possible clinical implications. We highlight how this cancer-related ribosome biogenesis, both at quantitative and qualitative levels, can lead to the synthesis of ribosomes favoring the translation of mRNAs encoding hyperproliferative and survival factors. We also discuss whether cancer-related ribosome biogenesis is a mere consequence of cancer progression or is a causal factor in CRC, and how altered ribosome biogenesis pathways can represent effective targets to kill CRC cells. The association between exacerbated CRC cell growth and alteration of specific steps of ribosome biogenesis is highlighted as a key driver of tumorigenesis, providing promising perspectives for the implementation of predictive biomarkers and the development of new therapeutic drugs.https://www.mdpi.com/2073-4409/9/11/2361ribosomecolorectalrDNArRNAtranslationtargeting |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sophie Nait Slimane Virginie Marcel Tanguy Fenouil Frédéric Catez Jean-Christophe Saurin Philippe Bouvet Jean-Jacques Diaz Hichem C. Mertani |
spellingShingle |
Sophie Nait Slimane Virginie Marcel Tanguy Fenouil Frédéric Catez Jean-Christophe Saurin Philippe Bouvet Jean-Jacques Diaz Hichem C. Mertani Ribosome Biogenesis Alterations in Colorectal Cancer Cells ribosome colorectal rDNA rRNA translation targeting |
author_facet |
Sophie Nait Slimane Virginie Marcel Tanguy Fenouil Frédéric Catez Jean-Christophe Saurin Philippe Bouvet Jean-Jacques Diaz Hichem C. Mertani |
author_sort |
Sophie Nait Slimane |
title |
Ribosome Biogenesis Alterations in Colorectal Cancer |
title_short |
Ribosome Biogenesis Alterations in Colorectal Cancer |
title_full |
Ribosome Biogenesis Alterations in Colorectal Cancer |
title_fullStr |
Ribosome Biogenesis Alterations in Colorectal Cancer |
title_full_unstemmed |
Ribosome Biogenesis Alterations in Colorectal Cancer |
title_sort |
ribosome biogenesis alterations in colorectal cancer |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-10-01 |
description |
Many studies have focused on understanding the regulation and functions of aberrant protein synthesis in colorectal cancer (CRC), leaving the ribosome, its main effector, relatively underappreciated in CRC. The production of functional ribosomes is initiated in the nucleolus, requires coordinated ribosomal RNA (rRNA) processing and ribosomal protein (RP) assembly, and is frequently hyperactivated to support the needs in protein synthesis essential to withstand unremitting cancer cell growth. This elevated ribosome production in cancer cells includes a strong alteration of ribosome biogenesis homeostasis that represents one of the hallmarks of cancer cells. None of the ribosome production steps escape this cancer-specific dysregulation. This review summarizes the early and late steps of ribosome biogenesis dysregulations described in CRC cell lines, intestinal organoids, CRC stem cells and mouse models, and their possible clinical implications. We highlight how this cancer-related ribosome biogenesis, both at quantitative and qualitative levels, can lead to the synthesis of ribosomes favoring the translation of mRNAs encoding hyperproliferative and survival factors. We also discuss whether cancer-related ribosome biogenesis is a mere consequence of cancer progression or is a causal factor in CRC, and how altered ribosome biogenesis pathways can represent effective targets to kill CRC cells. The association between exacerbated CRC cell growth and alteration of specific steps of ribosome biogenesis is highlighted as a key driver of tumorigenesis, providing promising perspectives for the implementation of predictive biomarkers and the development of new therapeutic drugs. |
topic |
ribosome colorectal rDNA rRNA translation targeting |
url |
https://www.mdpi.com/2073-4409/9/11/2361 |
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