Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

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.

Keywords: Colorectal cancer, β-catenin pathway, Tumor stroma, Tumor microenvironment factors, Cancer progression, Drug resistance

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.