Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells

Abstract

The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through β-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, depending on the cellular context. This review summarizes the available information on the role of the Wnt/β-catenin pathway and its crosstalk with other signaling pathways in apoptosis induction in cancer cells and presents a modified dual-signal model for the function of β-catenin. Understanding the proapoptotic mechanisms induced by the Wnt/β-catenin pathway could open new therapeutic opportunities.

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

“…197 Small molecules inhibit the overexpression of the Wnt/β-catenin pathway in cancer cells to regulate cell proliferation and apoptosis. 198 C644-0303, a small-molecule inhibitor, was shown to suppress the Wnt/β-catenin pathway to inhibit cell migration and induce apoptosis in CRC cell lines. 199 Obatoclax as a pan-Bcl-2 inhibitor had been shown to obstruct BH3-mediated binding of BH3-only proteins or Bax/Bak to induce apoptosis.…”

Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer

“…This is in accordance with an observed decrease in the number of β-catenin-positive cases and the intensity of expression in parallel with a reduction in tumor differentiation in an immunohistochemical study on oral squamous cell carcinoma [ 43 ]. Notably, recent evidence has highlighted the tumor-suppressing properties of β-catenin, which might explain the aforementioned finding of its inverse association with tumor grade and drug resistance [ 44 ]. Nevertheless, the exact role of β-catenin in cancer development and progression remains to be elaborated, since an association between β-catenin pathway activation and drug resistance as well as inferior outcomes has also been reported for some malignancies [ 12 , 45 , 46 ].…”

Sempervirine Inhibits Proliferation and Promotes Apoptosis by Regulating Wnt/β-Catenin Pathway in Human Hepatocellular Carcinoma

“…The over activation of Wnt pathway can induce the occurrence of primary liver cancer in mice. In patients with liver cancer, Wnt pathway is the signal pathway with the highest mutation rate except p53 ( Trejo-Solis et al, 2021 ). Wnt pathway inhibitors can not only inhibit the growth of HCC cells, but also reduce the drug resistance of cells and sensitize chemotherapeutic drugs ( Vilchez et al, 2016 ).…”