Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanism in lung epithelial cells

Journal Article · Wed May 15 04:00:00 EDT 2013 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2013.03.006· OSTI ID:22285297

Ding, Song-Ze ^[1]; Yang, Yu-Xiu; Li, Xiu-Ling ^[1]; Michelli-Rivera, Audrey ^[2]; Han, Shuang-Yin ^[1]; Wang, Lei; Pratheeshkumar, Poyil; Wang, Xin; Lu, Jian; Yin, Yuan-Qin; Budhraja, Amit; Hitron, Andrew J. ^[2]

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1. Department of Internal Medicine, Henan Provincial People’s Hospital, Zhengzhou University, Wei-Wu Road, Zhengzhou, Henan 450000 (China)
2. Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

Hexavalent chromium [Cr(VI)] is an important human carcinogen associated with pulmonary diseases and lung cancer. Exposure to Cr(VI) induces DNA damage, cell morphological change and malignant transformation in human lung epithelial cells. Despite extensive studies, the molecular mechanisms remain elusive, it is also not known if Cr(VI)-induced transformation might accompany with invasive properties to facilitate metastasis. We aimed to study Cr(VI)-induced epithelial–mesenchymal transition (EMT) and invasion during oncogenic transformation in lung epithelial cells. The results showed that Cr(VI) at low doses represses E-cadherin mRNA and protein expression, enhances mesenchymal marker vimentin expression and transforms the epithelial cell into fibroblastoid morphology. Cr(VI) also increases cell invasion and promotes colony formation. Further studies indicated that Cr(VI) uses multiple mechanisms to repress E-cadherin expression, including activation of E-cadherin repressors such as Slug, ZEB1, KLF8 and enhancement the binding of HDAC1 in E-cadherin gene promoter, but DNA methylation is not responsible for the loss of E-cadherin. Catalase reduces Cr(VI)-induced E-cadherin and vimentin protein expression, attenuates cell invasion in matrigel and colony formation on soft agar. These results demonstrate that exposure to a common human carcinogen, Cr(VI), induces EMT and invasion during oncogenic transformation in lung epithelial cells and implicate in cancer metastasis and prevention. - Graphical abstract: Epithelial–mesenchymal transition during oncogenic transformation induced by hexavalent chromium involves reactive oxygen species-dependent mechanisms in lung epithelial cells. - Highlights: • We study if Cr(VI) might induce EMT and invasion in epithelial cells. • Cr(VI) induces EMT by altering E-cadherin and vimentin expression. • It also increases cell invasion and promotes oncogenic transformation. • Catalase reduces Cr(VI)-induced EMT, invasion and transformation.

• OSTI ID: 22285297
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 1 Vol. 269; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENS
CATALASE
CHROMIUM
COLONY FORMATION
DNA
DNA DAMAGES
LUNGS
MESSENGER-RNA
METASTASES
METHYLATION
NEOPLASMS
ONCOGENIC TRANSFORMATIONS
OXYGEN