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Recent research suggests that cadmium (Cd) and other metals disrupt normal cellular homeostasis through epigenetic changes, particularly modifying the \u03b2-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 \u03b2-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 \u03b2-catenin pathway exacerbate Cd\u2019s 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 \u03b2-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 \u03b2-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.<\/jats:p>","DOI":"10.3389\/fcell.2026.1808500","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:49:14Z","timestamp":1776836954000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Epigenetic regulation of the \u03b2-catenin pathway in cadmium-induced colorectal cancer progression and chemoresistance"],"prefix":"10.3389","volume":"14","author":[{"given":"Rajkumar","family":"Prabhakaran","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Karpagam Academy of Higher Education (Deemed to be University)","place":["Coimbatore, Tamil Nadu, Ethiopia"]},{"name":"Centre for Cancer Research, Karpagam Academy of Higher Education","place":["Coimbatore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkumar","family":"Muthu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Sri Kaliswari College (Autonomous)","place":["Sivakas, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthikeyan","family":"Mahendran","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University","place":["Chennai, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajkumar","family":"Thamarai","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Manonmaniam Sundaranar University","place":["Tirunelveli, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatesh","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Manonmaniam Sundaranar University","place":["Tirunelveli, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorimuthu","family":"Revathi","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Centre for Global Health Research, Saveetha Medical College and Hospital","place":["Chennai, Tamilnadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubramanian","family":"Velramar","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Chhattisgarh","place":["Raipur, Chhattisgarh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanmugapriya","family":"Dharani","sequence":"additional","affiliation":[{"name":"Vicerrector\u00eda de Investigaci\u00f3n y Postgrado, Universidad de La Serena","place":["La Serena, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balachandran","family":"Ruthramurthy","sequence":"additional","affiliation":[{"name":"Department of ECE, Adama Science and Technology University","place":["Adama, Ethiopia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"682593","DOI":"10.3389\/fcell.2021.682593","article-title":"Epigenetic reprogramming mediated by maternal diet rich in omega-3 fatty acids protects from breast cancer development in F1 offspring","volume":"9","author":"Abbas","year":"2021","journal-title":"Front. 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