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Tumor Milieu Controlled by RB Tumor Suppressor
The RB gene is one of the most frequently mutated genes in human cancers. Canonically, RB exerts its tumor suppressive activity through the regulation of the G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. However, aberration of the RB gene is m...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177274/ https://www.ncbi.nlm.nih.gov/pubmed/32244804 http://dx.doi.org/10.3390/ijms21072450 |
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author | Kitajima, Shunsuke Li, Fengkai Takahashi, Chiaki |
author_facet | Kitajima, Shunsuke Li, Fengkai Takahashi, Chiaki |
author_sort | Kitajima, Shunsuke |
collection | PubMed |
description | The RB gene is one of the most frequently mutated genes in human cancers. Canonically, RB exerts its tumor suppressive activity through the regulation of the G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. However, aberration of the RB gene is most commonly detected in tumors when they gain more aggressive phenotypes, including metastatic activity or drug resistance, rather than accelerated proliferation. This implicates RB controls’ malignant progression to a considerable extent in a cell cycle-independent manner. In this review, we highlight the multifaceted functions of the RB protein in controlling tumor lineage plasticity, metabolism, and the tumor microenvironment (TME), with a focus on the mechanism whereby RB controls the TME. In brief, RB inactivation in several types of cancer cells enhances production of pro-inflammatory cytokines, including CCL2, through upregulation of mitochondrial reactive oxygen species (ROS) production. These factors not only accelerate the growth of cancer cells in a cell-autonomous manner, but also stimulate non-malignant cells in the TME to generate a pro-tumorigenic niche in a non-cell-autonomous manner. Here, we discuss the biological and pathological significance of the non-cell-autonomous functions of RB and attempt to predict their potential clinical relevance to cancer immunotherapy. |
format | Online Article Text |
id | pubmed-7177274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71772742020-04-28 Tumor Milieu Controlled by RB Tumor Suppressor Kitajima, Shunsuke Li, Fengkai Takahashi, Chiaki Int J Mol Sci Review The RB gene is one of the most frequently mutated genes in human cancers. Canonically, RB exerts its tumor suppressive activity through the regulation of the G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. However, aberration of the RB gene is most commonly detected in tumors when they gain more aggressive phenotypes, including metastatic activity or drug resistance, rather than accelerated proliferation. This implicates RB controls’ malignant progression to a considerable extent in a cell cycle-independent manner. In this review, we highlight the multifaceted functions of the RB protein in controlling tumor lineage plasticity, metabolism, and the tumor microenvironment (TME), with a focus on the mechanism whereby RB controls the TME. In brief, RB inactivation in several types of cancer cells enhances production of pro-inflammatory cytokines, including CCL2, through upregulation of mitochondrial reactive oxygen species (ROS) production. These factors not only accelerate the growth of cancer cells in a cell-autonomous manner, but also stimulate non-malignant cells in the TME to generate a pro-tumorigenic niche in a non-cell-autonomous manner. Here, we discuss the biological and pathological significance of the non-cell-autonomous functions of RB and attempt to predict their potential clinical relevance to cancer immunotherapy. MDPI 2020-04-01 /pmc/articles/PMC7177274/ /pubmed/32244804 http://dx.doi.org/10.3390/ijms21072450 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kitajima, Shunsuke Li, Fengkai Takahashi, Chiaki Tumor Milieu Controlled by RB Tumor Suppressor |
title | Tumor Milieu Controlled by RB Tumor Suppressor |
title_full | Tumor Milieu Controlled by RB Tumor Suppressor |
title_fullStr | Tumor Milieu Controlled by RB Tumor Suppressor |
title_full_unstemmed | Tumor Milieu Controlled by RB Tumor Suppressor |
title_short | Tumor Milieu Controlled by RB Tumor Suppressor |
title_sort | tumor milieu controlled by rb tumor suppressor |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177274/ https://www.ncbi.nlm.nih.gov/pubmed/32244804 http://dx.doi.org/10.3390/ijms21072450 |
work_keys_str_mv | AT kitajimashunsuke tumormilieucontrolledbyrbtumorsuppressor AT lifengkai tumormilieucontrolledbyrbtumorsuppressor AT takahashichiaki tumormilieucontrolledbyrbtumorsuppressor |