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Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer
Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in...
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/PMC7761347/ https://www.ncbi.nlm.nih.gov/pubmed/33266015 http://dx.doi.org/10.3390/biom10121617 |
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author | Scalia, Pierluigi Giordano, Antonio Martini, Caroline Williams, Stephen J. |
author_facet | Scalia, Pierluigi Giordano, Antonio Martini, Caroline Williams, Stephen J. |
author_sort | Scalia, Pierluigi |
collection | PubMed |
description | Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform- and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors. |
format | Online Article Text |
id | pubmed-7761347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77613472020-12-26 Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer Scalia, Pierluigi Giordano, Antonio Martini, Caroline Williams, Stephen J. Biomolecules Review Insulin receptor (IR) and IR-related signaling defects have been shown to trigger insulin-resistance in insulin-dependent cells and ultimately to give rise to type 2 diabetes in mammalian organisms. IR expression is ubiquitous in mammalian tissues, and its over-expression is also a common finding in cancerous cells. This latter finding has been shown to associate with both a relative and absolute increase in IR isoform-A (IR-A) expression, missing 12 aa in its EC subunit corresponding to exon 11. Since IR-A is a high-affinity transducer of Insulin-like Growth Factor-II (IGF-II) signals, a growth factor is often secreted by cancer cells; such event offers a direct molecular link between IR-A/IR-B increased ratio in insulin resistance states (obesity and type 2 diabetes) and the malignant advantage provided by IGF-II to solid tumors. Nonetheless, recent findings on the biological role of isoforms for cellular signaling components suggest that the preferential expression of IR isoform-A may be part of a wider contextual isoform-expression switch in downstream regulatory factors, potentially enhancing IR-dependent oncogenic effects. The present review focuses on the role of isoform- and paralog-dependent variability in the IR and downstream cellular components playing a potential role in the modulation of the IR-A signaling related to the changes induced by insulin-resistance-linked conditions as well as to their relationship with the benign versus malignant transition in underlying solid tumors. MDPI 2020-11-30 /pmc/articles/PMC7761347/ /pubmed/33266015 http://dx.doi.org/10.3390/biom10121617 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 Scalia, Pierluigi Giordano, Antonio Martini, Caroline Williams, Stephen J. Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer |
title | Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer |
title_full | Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer |
title_fullStr | Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer |
title_full_unstemmed | Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer |
title_short | Isoform- and Paralog-Switching in IR-Signaling: When Diabetes Opens the Gates to Cancer |
title_sort | isoform- and paralog-switching in ir-signaling: when diabetes opens the gates to cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761347/ https://www.ncbi.nlm.nih.gov/pubmed/33266015 http://dx.doi.org/10.3390/biom10121617 |
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