Metal carcinogen exposure induces cancer stem cell-like property through epigenetic reprograming: A novel mechanism of metal carcinogenesis

Arsenic, cadmium, nickel and hexavalent chromium are among the most common environmental pollutants and potent carcinogens. Chronic exposure to these metals causes various types of cancer in humans, representing a significant environmental health issue. Although under active investigation, the mechanisms of metal carcinogenesis have not been clearly defined. One common feature of these metal carcinogens is that they are all able to cause various epigenetic dysregulations, which are believed to play important roles in their carcinogenicity. However, how metal carcinogen-caused epigenetic dysregulation contributes to metal carcinogenesis remains largely unknown. The evolution of cancer stem cell (CSC) theory has opened exciting new avenues for studying the mechanism of metal carcinogenesis. Increasing evidence indicates that chronic metal carcinogen exposure produces CSC-like cells through dysregulated epigenetic mechanisms. This review will first provide some brief introductions about CSC, epigenetics and epigenetic regulation of CSCs; then summarize progresses in recent studies on metal carcinogen-induced CSC-like property through epigenetic reprograming as a novel mechanism of metal carcinogenesis. Some perspectives for future studies in this field are also presented.