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Discoidin Domain Receptors: Potential Actors and Targets in Cancer
The extracellular matrix critically controls cancer cell behavior by inducing several signaling pathways through cell membrane receptors. Besides conferring structural properties to tissues around the tumor, the extracellular matrix is able to regulate cell proliferation, survival, migration, and in...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789497/ https://www.ncbi.nlm.nih.gov/pubmed/27014069 http://dx.doi.org/10.3389/fphar.2016.00055 |
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author | Rammal, Hassan Saby, Charles Magnien, Kevin Van-Gulick, Laurence Garnotel, Roselyne Buache, Emilie El Btaouri, Hassan Jeannesson, Pierre Morjani, Hamid |
author_facet | Rammal, Hassan Saby, Charles Magnien, Kevin Van-Gulick, Laurence Garnotel, Roselyne Buache, Emilie El Btaouri, Hassan Jeannesson, Pierre Morjani, Hamid |
author_sort | Rammal, Hassan |
collection | PubMed |
description | The extracellular matrix critically controls cancer cell behavior by inducing several signaling pathways through cell membrane receptors. Besides conferring structural properties to tissues around the tumor, the extracellular matrix is able to regulate cell proliferation, survival, migration, and invasion. Among these receptors, the integrins family constitutes a major class of receptors that mediate cell interactions with extracellular matrix components. Twenty years ago, a new class of extracellular matrix receptors has been discovered. These tyrosine kinase receptors are the two discoidin domain receptors DDR1 and DDR2. DDR1 was first identified in the Dictyostelium discoideum and was shown to mediate cell aggregation. DDR2 shares highly conserved sequences with DDR1. Both receptors are activated upon binding to collagen, one of the most abundant proteins in extracellular matrix. While DDR2 can only be activated by fibrillar collagen, particularly types I and III, DDR1 is mostly activated by type I and IV collagens. In contrast with classical growth factor tyrosine kinase receptors which display a rapid and transient activation, DDR1 and DDR2 are unique in that they exhibit delayed and sustained receptor phosphorylation upon binding to collagen. Recent studies have reported differential expression and mutations of DDR1 and DDR2 in several cancer types and indicate clearly that these receptors have to be taken into account as new players in the different aspects of tumor progression, from non-malignant to highly malignant and invasive stages. This review will discuss the current knowledge on the role of DDR1 and DDR2 in malignant transformation, cell proliferation, epithelial to mesenchymal transition, migratory, and invasive processes, and finally the modulation of the response to chemotherapy. These new insights suggest that DDR1 and DDR2 are new potential targets in cancer therapy. |
format | Online Article Text |
id | pubmed-4789497 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47894972016-03-24 Discoidin Domain Receptors: Potential Actors and Targets in Cancer Rammal, Hassan Saby, Charles Magnien, Kevin Van-Gulick, Laurence Garnotel, Roselyne Buache, Emilie El Btaouri, Hassan Jeannesson, Pierre Morjani, Hamid Front Pharmacol Pharmacology The extracellular matrix critically controls cancer cell behavior by inducing several signaling pathways through cell membrane receptors. Besides conferring structural properties to tissues around the tumor, the extracellular matrix is able to regulate cell proliferation, survival, migration, and invasion. Among these receptors, the integrins family constitutes a major class of receptors that mediate cell interactions with extracellular matrix components. Twenty years ago, a new class of extracellular matrix receptors has been discovered. These tyrosine kinase receptors are the two discoidin domain receptors DDR1 and DDR2. DDR1 was first identified in the Dictyostelium discoideum and was shown to mediate cell aggregation. DDR2 shares highly conserved sequences with DDR1. Both receptors are activated upon binding to collagen, one of the most abundant proteins in extracellular matrix. While DDR2 can only be activated by fibrillar collagen, particularly types I and III, DDR1 is mostly activated by type I and IV collagens. In contrast with classical growth factor tyrosine kinase receptors which display a rapid and transient activation, DDR1 and DDR2 are unique in that they exhibit delayed and sustained receptor phosphorylation upon binding to collagen. Recent studies have reported differential expression and mutations of DDR1 and DDR2 in several cancer types and indicate clearly that these receptors have to be taken into account as new players in the different aspects of tumor progression, from non-malignant to highly malignant and invasive stages. This review will discuss the current knowledge on the role of DDR1 and DDR2 in malignant transformation, cell proliferation, epithelial to mesenchymal transition, migratory, and invasive processes, and finally the modulation of the response to chemotherapy. These new insights suggest that DDR1 and DDR2 are new potential targets in cancer therapy. Frontiers Media S.A. 2016-03-14 /pmc/articles/PMC4789497/ /pubmed/27014069 http://dx.doi.org/10.3389/fphar.2016.00055 Text en Copyright © 2016 Rammal, Saby, Magnien, Van-Gulick, Garnotel, Buache, El Btaouri, Jeannesson and Morjani. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Rammal, Hassan Saby, Charles Magnien, Kevin Van-Gulick, Laurence Garnotel, Roselyne Buache, Emilie El Btaouri, Hassan Jeannesson, Pierre Morjani, Hamid Discoidin Domain Receptors: Potential Actors and Targets in Cancer |
title | Discoidin Domain Receptors: Potential Actors and Targets in Cancer |
title_full | Discoidin Domain Receptors: Potential Actors and Targets in Cancer |
title_fullStr | Discoidin Domain Receptors: Potential Actors and Targets in Cancer |
title_full_unstemmed | Discoidin Domain Receptors: Potential Actors and Targets in Cancer |
title_short | Discoidin Domain Receptors: Potential Actors and Targets in Cancer |
title_sort | discoidin domain receptors: potential actors and targets in cancer |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4789497/ https://www.ncbi.nlm.nih.gov/pubmed/27014069 http://dx.doi.org/10.3389/fphar.2016.00055 |
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