Short Linear Motifs in Colorectal Cancer Interactome and Tumorigenesis

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Dec 11

PMID 36496998

Authors

Candida Fasano

Valentina Grossi

Giovanna Forte

Cristiano Simone

Affiliations

Soon will be listed here.

Abstract

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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References

Li D, Zhang T, Lai J, Zhang J, Wang T, Ling Y . MicroRNA‑25/ATXN3 interaction regulates human colon cancer cell growth and migration. Mol Med Rep. 2019; 19(5):4213-4221. PMC: 6471560. DOI: 10.3892/mmr.2019.10090. View

Neduva V, Russell R . Peptides mediating interaction networks: new leads at last. Curr Opin Biotechnol. 2006; 17(5):465-71. DOI: 10.1016/j.copbio.2006.08.002. View

Jing X, Zeng H, Wang S, Xu J . A Web-Based Protocol for Interprotein Contact Prediction by Deep Learning. Methods Mol Biol. 2019; 2074:67-80. DOI: 10.1007/978-1-4939-9873-9_6. View

Yu X, Chini C, He M, Mer G, Chen J . The BRCT domain is a phospho-protein binding domain. Science. 2003; 302(5645):639-42. DOI: 10.1126/science.1088753. View

Zanzoni A, Spinelli L, Braham S, Brun C . Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence proteins. Microbiome. 2017; 5(1):89. PMC: 5551000. DOI: 10.1186/s40168-017-0307-1. View

Olkinuora A, Peltomaki P, Aaltonen L, Rajamaki K . From APC to the genetics of hereditary and familial colon cancer syndromes. Hum Mol Genet. 2021; 30(R2):R206-R224. PMC: 8490010. DOI: 10.1093/hmg/ddab208. View

Mi T, Merlin J, Deverasetty S, Gryk M, Bill T, Brooks A . Minimotif Miner 3.0: database expansion and significantly improved reduction of false-positive predictions from consensus sequences. Nucleic Acids Res. 2011; 40(Database issue):D252-60. PMC: 3245078. DOI: 10.1093/nar/gkr1189. View

A V S S, Sinha S, Donakonda S . Virus-host interaction analysis in colorectal cancer identifies core virus network signature and small molecules. Comput Struct Biotechnol J. 2022; 20:4025-4039. PMC: 9356043. DOI: 10.1016/j.csbj.2022.07.040. View

Samano-Sanchez H, Gibson T . Mimicry of Short Linear Motifs by Bacterial Pathogens: A Drugging Opportunity. Trends Biochem Sci. 2020; 45(6):526-544. DOI: 10.1016/j.tibs.2020.03.003. View

10.

Re A, Lecca P . On TD-WGcluster: Theoretical Foundations and Guidelines for the User. Methods Mol Biol. 2019; 2074:233-262. DOI: 10.1007/978-1-4939-9873-9_17. View

11.

El-Masry O, Goja A, Rateb M, Owaidah A, Alsamman K . RNA sequencing identified novel target genes for in breast and colon cancer cells. Sci Prog. 2021; 104(3):368504211032084. PMC: 10450698. DOI: 10.1177/00368504211032084. View

12.

Petsalaki E, Russell R . Peptide-mediated interactions in biological systems: new discoveries and applications. Curr Opin Biotechnol. 2008; 19(4):344-50. DOI: 10.1016/j.copbio.2008.06.004. View

13.

Wang H, Wang X, Zhang H, Deng T, Liu R, Liu Y . The HSF1/miR-135b-5p axis induces protective autophagy to promote oxaliplatin resistance through the MUL1/ULK1 pathway in colorectal cancer. Oncogene. 2021; 40(28):4695-4708. DOI: 10.1038/s41388-021-01898-z. View

14.

Nicholson R, Gee J, Harper M . EGFR and cancer prognosis. Eur J Cancer. 2001; 37 Suppl 4:S9-15. DOI: 10.1016/s0959-8049(01)00231-3. View

15.

Letai A, Bassik M, Walensky L, Sorcinelli M, Weiler S, Korsmeyer S . Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002; 2(3):183-92. DOI: 10.1016/s1535-6108(02)00127-7. View

16.

Davey N, Edwards R, Shields D . Computational identification and analysis of protein short linear motifs. Front Biosci (Landmark Ed). 2010; 15(3):801-25. DOI: 10.2741/3647. View

17.

Chen L, Borcherds W, Wu S, Becker A, Schonbrunn E, Daughdrill G . Autoinhibition of MDMX by intramolecular p53 mimicry. Proc Natl Acad Sci U S A. 2015; 112(15):4624-9. PMC: 4403185. DOI: 10.1073/pnas.1420833112. View

18.

Davey N, Van Roey K, Weatheritt R, Toedt G, Uyar B, Altenberg B . Attributes of short linear motifs. Mol Biosyst. 2011; 8(1):268-81. DOI: 10.1039/c1mb05231d. View

19.

Santos G, Ganesan A, Emery F . Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule. ChemMedChem. 2016; 11(20):2245-2251. DOI: 10.1002/cmdc.201600288. View

20.

Peserico A, Germani A, Sanese P, Barbosa A, Di Virgilio V, Fittipaldi R . A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth. J Cell Physiol. 2015; 230(10):2447-2460. PMC: 4988495. DOI: 10.1002/jcp.24975. View