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Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis

Colorectal tumorigenesis is driven by alterations in genes and proteins responsible for cancer initiation, progression, and invasion. This multistage process is based on a dense network of protein–protein interactions (PPIs) that become dysregulated as a result of changes in various cell signaling e...

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Autores principales: Fasano, Candida, Grossi, Valentina, Forte, Giovanna, Simone, Cristiano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737320/
https://www.ncbi.nlm.nih.gov/pubmed/36496998
http://dx.doi.org/10.3390/cells11233739
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author Fasano, Candida
Grossi, Valentina
Forte, Giovanna
Simone, Cristiano
author_facet Fasano, Candida
Grossi, Valentina
Forte, Giovanna
Simone, Cristiano
author_sort Fasano, Candida
collection PubMed
description Colorectal tumorigenesis is driven by alterations in genes and proteins responsible for cancer initiation, progression, and invasion. This multistage process is based on a dense network of protein–protein interactions (PPIs) that become dysregulated as a result of changes in various cell signaling effectors. PPIs in signaling and regulatory networks are known to be mediated by short linear motifs (SLiMs), which are conserved contiguous regions of 3–10 amino acids within interacting protein domains. SLiMs are the minimum sequences required for modulating cellular PPI networks. Thus, several in silico approaches have been developed to predict and analyze SLiM-mediated PPIs. In this review, we focus on emerging evidence supporting a crucial role for SLiMs in driver pathways that are disrupted in colorectal cancer (CRC) tumorigenesis and related PPI network alterations. As a result, SLiMs, along with short peptides, are attracting the interest of researchers to devise small molecules amenable to be used as novel anti-CRC targeted therapies. Overall, the characterization of SLiMs mediating crucial PPIs in CRC may foster the development of more specific combined pharmacological approaches.
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spelling pubmed-97373202022-12-11 Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis Fasano, Candida Grossi, Valentina Forte, Giovanna Simone, Cristiano Cells Review Colorectal tumorigenesis is driven by alterations in genes and proteins responsible for cancer initiation, progression, and invasion. This multistage process is based on a dense network of protein–protein interactions (PPIs) that become dysregulated as a result of changes in various cell signaling effectors. PPIs in signaling and regulatory networks are known to be mediated by short linear motifs (SLiMs), which are conserved contiguous regions of 3–10 amino acids within interacting protein domains. SLiMs are the minimum sequences required for modulating cellular PPI networks. Thus, several in silico approaches have been developed to predict and analyze SLiM-mediated PPIs. In this review, we focus on emerging evidence supporting a crucial role for SLiMs in driver pathways that are disrupted in colorectal cancer (CRC) tumorigenesis and related PPI network alterations. As a result, SLiMs, along with short peptides, are attracting the interest of researchers to devise small molecules amenable to be used as novel anti-CRC targeted therapies. Overall, the characterization of SLiMs mediating crucial PPIs in CRC may foster the development of more specific combined pharmacological approaches. MDPI 2022-11-23 /pmc/articles/PMC9737320/ /pubmed/36496998 http://dx.doi.org/10.3390/cells11233739 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fasano, Candida
Grossi, Valentina
Forte, Giovanna
Simone, Cristiano
Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis
title Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis
title_full Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis
title_fullStr Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis
title_full_unstemmed Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis
title_short Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis
title_sort short linear motifs in colorectal cancer interactome and tumorigenesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9737320/
https://www.ncbi.nlm.nih.gov/pubmed/36496998
http://dx.doi.org/10.3390/cells11233739
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