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Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer

Teneurins are large transmembrane proteins originally identified in Drosophila. Their essential role in development of the central nervous system is conserved throughout species, and evidence supports their involvement in organogenesis of additional tissues. Homophilic and heterophilic interactions...

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Autores principales: Rebolledo-Jaramillo, Boris, Ziegler, Annemarie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297388/
https://www.ncbi.nlm.nih.gov/pubmed/30618566
http://dx.doi.org/10.3389/fnins.2018.00937
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author Rebolledo-Jaramillo, Boris
Ziegler, Annemarie
author_facet Rebolledo-Jaramillo, Boris
Ziegler, Annemarie
author_sort Rebolledo-Jaramillo, Boris
collection PubMed
description Teneurins are large transmembrane proteins originally identified in Drosophila. Their essential role in development of the central nervous system is conserved throughout species, and evidence supports their involvement in organogenesis of additional tissues. Homophilic and heterophilic interactions between Teneurin paralogues mediate cellular adhesion in crucial processes such as neuronal pathfinding and synaptic organization. At the molecular level, Teneurins are proteolytically processed into distinct subdomains that have been implicated in extracellular and intracellular signaling, and in transcriptional regulation. Phylogenetic studies have shown a high degree of intra- and interspecies conservation of Teneurin genes. Accordingly, the occurrence of genetic variants has been associated with functional and phenotypic alterations in experimental systems, and with some inherited or sporadic conditions. Recently, tumor-related variations in Teneurin gene expression have been associated with patient survival in different cancers. Although these findings were incidental and molecular mechanisms were not addressed, they suggested a potential utility of Teneurin transcript levels as biomarkers for disease prognosis. Mutations and chromosomal alterations affecting Teneurin genes have been found occasionally in tumors, but literature remains scarce. The analysis of open-access molecular and clinical datasets derived from large oncologic cohorts provides an invaluable resource for the identification of additional somatic mutations. However, Teneurin variants have not been classified in terms of pathogenic risk and their phenotypic impact remains unknown. On this basis, is it plausible to hypothesize that Teneurins play a role in carcinogenesis? Does current evidence support a tumor suppressive or rather oncogenic function for these proteins? Here, we comprehensively discuss available literature with integration of molecular evidence retrieved from open-access databases. We show that Teneurins undergo somatic changes comparable to those of well-established cancer genes, and discuss their involvement in cancer-related signaling pathways. Current data strongly suggest a functional contribution of Teneurins to human carcinogenesis.
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spelling pubmed-62973882019-01-07 Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer Rebolledo-Jaramillo, Boris Ziegler, Annemarie Front Neurosci Neuroscience Teneurins are large transmembrane proteins originally identified in Drosophila. Their essential role in development of the central nervous system is conserved throughout species, and evidence supports their involvement in organogenesis of additional tissues. Homophilic and heterophilic interactions between Teneurin paralogues mediate cellular adhesion in crucial processes such as neuronal pathfinding and synaptic organization. At the molecular level, Teneurins are proteolytically processed into distinct subdomains that have been implicated in extracellular and intracellular signaling, and in transcriptional regulation. Phylogenetic studies have shown a high degree of intra- and interspecies conservation of Teneurin genes. Accordingly, the occurrence of genetic variants has been associated with functional and phenotypic alterations in experimental systems, and with some inherited or sporadic conditions. Recently, tumor-related variations in Teneurin gene expression have been associated with patient survival in different cancers. Although these findings were incidental and molecular mechanisms were not addressed, they suggested a potential utility of Teneurin transcript levels as biomarkers for disease prognosis. Mutations and chromosomal alterations affecting Teneurin genes have been found occasionally in tumors, but literature remains scarce. The analysis of open-access molecular and clinical datasets derived from large oncologic cohorts provides an invaluable resource for the identification of additional somatic mutations. However, Teneurin variants have not been classified in terms of pathogenic risk and their phenotypic impact remains unknown. On this basis, is it plausible to hypothesize that Teneurins play a role in carcinogenesis? Does current evidence support a tumor suppressive or rather oncogenic function for these proteins? Here, we comprehensively discuss available literature with integration of molecular evidence retrieved from open-access databases. We show that Teneurins undergo somatic changes comparable to those of well-established cancer genes, and discuss their involvement in cancer-related signaling pathways. Current data strongly suggest a functional contribution of Teneurins to human carcinogenesis. Frontiers Media S.A. 2018-12-11 /pmc/articles/PMC6297388/ /pubmed/30618566 http://dx.doi.org/10.3389/fnins.2018.00937 Text en Copyright © 2018 Rebolledo-Jaramillo and Ziegler. 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) and the copyright owner(s) 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 Neuroscience
Rebolledo-Jaramillo, Boris
Ziegler, Annemarie
Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer
title Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer
title_full Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer
title_fullStr Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer
title_full_unstemmed Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer
title_short Teneurins: An Integrative Molecular, Functional, and Biomedical Overview of Their Role in Cancer
title_sort teneurins: an integrative molecular, functional, and biomedical overview of their role in cancer
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297388/
https://www.ncbi.nlm.nih.gov/pubmed/30618566
http://dx.doi.org/10.3389/fnins.2018.00937
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