Epigenetic regulation of the β-catenin pathway in cadmium-induced colorectal cancer progression and chemoresistance.

Colorectal cancer (CRC) has become a global health issue, as exposure to toxic metals (lead, chromium, cadmium, aluminum, copper, arsenic, and mercury) has all been implicated in its development and progression through interference with the mechanisms of cell proliferation and death. Recent research suggests that cadmium (Cd) and other metals disrupt normal cellular homeostasis through epigenetic changes, particularly modifying the β-catenin signaling pathway, an important key regulator of cell proliferation, differentiation, and survival. This study explores and examines the molecular mechanisms of Cd-induced changes in DNA methylation, histone acetylation, and non-coding RNA, which increase β-catenin activation and translocation into the nucleus. Such atypical epigenetic alterations promote oncogene transcriptional upregulation and survival pathways to promote tumorigenesis and non-response to chemotherapy agents. Altered epigenome regulation and dysregulation of the β-catenin pathway exacerbate Cd's oxidative stress and inflammatory capacities, which in turn lead to tumor-promoting microenvironment capabilities. The alterations uncovered with Cd exposure and epigenetic reprogramming, as well as the altered β-catenin signaling pathways, offer additional information regarding the molecular etiology of Cd-induced CRC. This review also suggests new possible treatments involving epigenetic regulators and β-catenin signaling components as exciting therapeutic approaches to address chemotherapy resistance and improve treatment outcomes for patients with colorectal cancer who have previously been exposed to heavy metals.