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Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment

Transforming growth factor-beta (TGF-β) signaling is one of the important cellular pathways that play key roles for tissue maintenance. In particular, it is important in the context of inflammation and tumorigenesis by modulating cell growth, differentiation, apoptosis, and homeostasis. TGF-β recept...

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Detalles Bibliográficos
Autores principales: Itatani, Yoshiro, Kawada, Kenji, Sakai, Yoshiharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929101/
https://www.ncbi.nlm.nih.gov/pubmed/31756952
http://dx.doi.org/10.3390/ijms20235822
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author Itatani, Yoshiro
Kawada, Kenji
Sakai, Yoshiharu
author_facet Itatani, Yoshiro
Kawada, Kenji
Sakai, Yoshiharu
author_sort Itatani, Yoshiro
collection PubMed
description Transforming growth factor-beta (TGF-β) signaling is one of the important cellular pathways that play key roles for tissue maintenance. In particular, it is important in the context of inflammation and tumorigenesis by modulating cell growth, differentiation, apoptosis, and homeostasis. TGF-β receptor type 2 (TGFBR2) mutations affected by a mismatch repair deficiency causes colorectal cancers (CRCs) with microsatellite instability, which is, however, associated with relatively better survival rates. On the other hand, loss of SMAD4, a transcription factor in the TGF-β superfamily signaling, promotes tumor progression. Loss of heterozygosity on chromosome 18 can case SMAD4-deficient CRC, which results in poorer patients’ survival. Such bidirectional phenomenon driven by TGF-β signaling insufficiency reflects the complexity of this signaling pathway in CRC. Moreover, recent understanding of CRC at the molecular level (consensus molecular subtype classification) provides deep insight into the important roles of TGF-β signaling in the tumor microenvironment. Here we focus on the TGF-β signaling in CRC and its interaction with the tumor microenvironment. We summarize the molecular mechanisms of CRC tumorigenesis and progression caused by disruption of TGF-β signaling by cancer epithelial cells and host stromal cells.
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spelling pubmed-69291012019-12-26 Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment Itatani, Yoshiro Kawada, Kenji Sakai, Yoshiharu Int J Mol Sci Review Transforming growth factor-beta (TGF-β) signaling is one of the important cellular pathways that play key roles for tissue maintenance. In particular, it is important in the context of inflammation and tumorigenesis by modulating cell growth, differentiation, apoptosis, and homeostasis. TGF-β receptor type 2 (TGFBR2) mutations affected by a mismatch repair deficiency causes colorectal cancers (CRCs) with microsatellite instability, which is, however, associated with relatively better survival rates. On the other hand, loss of SMAD4, a transcription factor in the TGF-β superfamily signaling, promotes tumor progression. Loss of heterozygosity on chromosome 18 can case SMAD4-deficient CRC, which results in poorer patients’ survival. Such bidirectional phenomenon driven by TGF-β signaling insufficiency reflects the complexity of this signaling pathway in CRC. Moreover, recent understanding of CRC at the molecular level (consensus molecular subtype classification) provides deep insight into the important roles of TGF-β signaling in the tumor microenvironment. Here we focus on the TGF-β signaling in CRC and its interaction with the tumor microenvironment. We summarize the molecular mechanisms of CRC tumorigenesis and progression caused by disruption of TGF-β signaling by cancer epithelial cells and host stromal cells. MDPI 2019-11-20 /pmc/articles/PMC6929101/ /pubmed/31756952 http://dx.doi.org/10.3390/ijms20235822 Text en © 2019 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
Itatani, Yoshiro
Kawada, Kenji
Sakai, Yoshiharu
Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment
title Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment
title_full Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment
title_fullStr Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment
title_full_unstemmed Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment
title_short Transforming Growth Factor-β Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment
title_sort transforming growth factor-β signaling pathway in colorectal cancer and its tumor microenvironment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929101/
https://www.ncbi.nlm.nih.gov/pubmed/31756952
http://dx.doi.org/10.3390/ijms20235822
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