Journal Article

Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis

Grossi, Valentina, Fasano, Candida, Simone, Cristiano, Forte, Giovanna

2022

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Analysis / Breast cancer / Cancer / cancer driver protein interactome / Carcinogenesis / Care and treatment / Cell cycle / Cell signaling / Colorectal cancer / colorectal cancer interactome / Colorectal Neoplasms - genetics / Cooperation / Databases, Protein / Diagnosis / Disease / Family medical history / Gene mutations / Genetic aspects / Health aspects / Humans / Liver cancer / Mutation / Peptides / Protein interaction / Protein Interaction Domains and Motifs / Protein-protein interactions / Proteins / Proteins - metabolism / Review / short linear motifs / SLiM-based small molecules / targeted therapy / Tumorigenesis