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

Zhishan Wang, Chengfeng Yang

Research output: Contribution to journalReview articlepeer-review

53 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalSeminars in Cancer Biology
Volume57
DOIs
StatePublished - Aug 2019

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [R01ES028256 and UK-CARES P30 Center Career Development Award to Z.W.; R01 ES026151 to C.Y. and UK NIEHS P30 center grant P30ES026529].

Funding Information:
This work was supported by the National Institutes of Health [ R01ES028256 and UK-CARES P30 Center Career Development Award to Z.W.; R01 ES026151 to C.Y. and UK NIEHS P30 center grant P30ES026529 ].

Funding Information:
The authors would like to thank Dr. Sandra Haslam (Michigan State University, East Lansing, Michigan, USA) for providing p53 knockout mice; Dr. Yujiro Higashi (Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan) for providing ZEB1 knockout mice; and the National Institutes of Health for providing support [R01ES028256 and UK-CARES P30 Center Career Development Award to Z.W.; R01 ES026151 to C.Y. and UK NIEHS P30 center grant P30ES026529].

Publisher Copyright:
© 2019 Elsevier Ltd

Keywords

  • Arsenic
  • Cadmium
  • Cancer stem cell
  • Cancer stem cell-like cell
  • Chromium
  • DNA methylation
  • Epigenetics
  • Histone posttranslational modification
  • Metal carcinogenesis
  • Nickel
  • Non-coding RNA
  • microRNA

ASJC Scopus subject areas

  • Cancer Research

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