Novoa Díaz MB, Martín MJ, Gentili C. Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance. World J Gastroenterol 2022; 28(26): 3027-3046 [PMID: 36051330 DOI: 10.3748/wjg.v28.i26.3027]
Corresponding Author of This Article
María Julia Martín, PhD, Research Assistant, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INBIOSUR (CONICET-UNS), San Juan 670, Bahía Blanca 8000, Argentina. julia.martin@uns.edu.ar
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jul 14, 2022; 28(26): 3027-3046 Published online Jul 14, 2022. doi: 10.3748/wjg.v28.i26.3027
Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance
María Belén Novoa Díaz, María Julia Martín, Claudia Gentili
María Belén Novoa Díaz, María Julia Martín, Claudia Gentili, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Argentina
María Julia Martín, Departamento de Química, Universidad Nacional del Sur (UNS)-INQUISUR (CONICET-UNS), Bahía Blanca 8000, Argentina
Author contributions: Novoa Díaz MB, Martín MJ, and Gentili C contributed to the conceptualization, methodology, investigation, formal analysis, and visualization, wrote the original draft, and edited the manuscript; Gentili C obtained the resources and oversaw the project administration and funding acquisition.
Supported byAgencia Nacional de Promoción Científica y Tecnológica, No. PICT-2013-1441; Consejo Nacional de Investigaciones Científicas y Técnicas, No. PIP11220150100350; Instituto Nacional del Cáncer Asistencia Financiera II, RESOL 493/14, No. 2002-4395-14-1; Instituto Nacional del Cáncer Asistencia Financiera III-2016-2017, RESOL-2016-1006-E-APN-MS, No. 2002-3862-16-1; and Universidad Nacional del Sur (PGI), Argentina, No. 24/B230 and No. 24/B303.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: María Julia Martín, PhD, Research Assistant, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INBIOSUR (CONICET-UNS), San Juan 670, Bahía Blanca 8000, Argentina. julia.martin@uns.edu.ar
Received: December 21, 2021 Peer-review started: December 21, 2021 First decision: March 10, 2022 Revised: April 29, 2022 Accepted: June 20, 2022 Article in press: June 20, 2022 Published online: July 14, 2022 Processing time: 203 Days and 18 Hours
Abstract
Colorectal cancer (CRC) continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies. Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer, including CRC. In many subtypes of CRC, hyperactivation of the β-catenin pathway is associated with mutations of the adenomatous polyposis coli gene. However, it can also be associated with other causes. In recent years, studies of the tumor microenvironment (TME) have demonstrated its importance in the development and progression of CRC. In this tumor nest, several cell types, structures, and biomolecules interact with neoplastic cells to pave the way for the spread of the disease. Cross-communications between tumor cells and the TME are then established primarily through paracrine factors, which trigger the activation of numerous signaling pathways. Crucial advances in the field of oncology have been made in the last decade. This Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness, focusing on cross-communication between CRC cells and the TME. Through this analysis, our main objective was to increase the understanding of this complex disease considering a more global context. Since many treatments for advanced CRC fail due to mechanisms involving chemoresistance, the data here exposed and analyzed are of great interest for the development of novel and effective therapies.
Core Tip: Currently, there is a high probability of failure in treatments for the advanced stages of colorectal cancer (CRC). For this reason, it is necessary to obtain a better understanding of CRC biology in a more global context for the future design of novel therapeutic approaches. The effects of the Wnt/β-catenin signaling pathway and the tumor microenvironment (TME) on the progression and chemoresistance of this disease were separately described in several review articles. Therefore, herein we comprehensively analyze the complex mechanisms of CRC chemoresistance triggered by TME factors that impact Wnt/β-catenin signaling.
