Biological functions and molecular interactions of Wnt/β-catenin in breast cancer: Revisiting signaling networks

Int J Biol Macromol. 2023 Mar 31:232:123377. doi: 10.1016/j.ijbiomac.2023.123377. Epub 2023 Jan 23.

Abstract

Changes in lifestyle such as physical activity and eating habits have been one of the main reasons for development of various diseases in modern world, especially cancer. However, role of genetic factors in initiation of cancer cannot be ignored and Wnt/β-catenin signaling is such factor that can affect tumor progression. Breast tumor is the most malignant tumor in females and it causes high mortality and morbidity around the world. The survival and prognosis of patients are not still desirable, although there have been advances in introducing new kinds of therapies and diagnosis. The present review provides an update of Wnt/β-catenin function in breast cancer malignancy. The upregulation of Wnt is commonly observed during progression of breast tumor and confirms that tumor cells are dependent on this pathway Wnt/β-catenin induction prevents apoptosis that is of importance for mediating drug resistance. Furthermore, Wnt/β-catenin signaling induces DNA damage repair in ameliorating radio-resistance. Wnt/β-catenin enhances proliferation and metastasis of breast tumor. Wnt/β-catenin induces EMT and elevates MMP expression. Furthermore, Wnt/β-catenin participates in tumor microenvironment remodeling and due to its tumor-promoting factor, drugs for its suppression have been developed. Different kinds of upstream mediators Wnt/β-catenin signaling in breast cancer have been recognized that their targeting is a therapeutic approach. Finally, Wnt/β-catenin can be considered as a biomarker in clinical trials.

Keywords: Breast cancer; Chemoresistance; Radio-resistance; Wnt/β-catenin signaling.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Transcriptional Activation
  • Tumor Microenvironment
  • Up-Regulation
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • beta Catenin