Wnt/β-catenin pathway as a link between therapy resistance-driven epithelial-mesenchymal transition and stemness in colorectal cancer

Cell Biol Int. 2025 Feb;49(2):154-160. doi: 10.1002/cbin.12270. Epub 2024 Dec 20.

Abstract

The high plasticity of cells undergoing epithelial-mesenchymal transition (EMT) promotes increased tumor heterogeneity, and its interaction with tumor-associated stromal cells appears to contribute to developing a stemness phenotype. Cells with these characteristics exhibit increased resistance to chemotherapy and radiotherapy, leading to disease relapse and metastasis. Here, we discuss the activation of the Wnt/β-catenin pathway in promoting EMT and stemness within the context of cellular resistance to these therapies. We discuss whether EMT and cancer stem cells (CSCs) function in conjunction, independently, or if a link is connecting their development. We further propose that this pathway is necessary to establish a connection between these two phenotypes. And suggest that it could hinder the rise of CSCs from treatment-induced EMT cells when inhibited. Understanding this cellular phenomenon might allow the development of new targeted therapies to improve clinical responses, particularly in colorectal cancer.

Keywords: Wnt/β‐catenin pathway; epithelial‐mesenchymal transition; stemness; therapy resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / therapy
  • Drug Resistance, Neoplasm*
  • Epithelial-Mesenchymal Transition* / physiology
  • Humans
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • beta Catenin