Arsenic Induces p62 Expression to Form a Positive Feedback Loop with Nrf2 in Human Epidermal Keratinocytes: Implications for Preventing Arsenic-Induced Skin Cancer
Year: 2017
Type: article
Abstract: Exposure to inorganic arsenic in contaminated drinking water poses an environmental public health threat for hundreds of millions of people in the US and around the world. Arsenic is a known carcinogen for skin cancer. However, the mechanism by which arsenic induces skin cancer remains poorly understood. Here, we have shown that arsenic induces p62 expression in an autophagy-independent manner in human HaCaT keratinocytes. In mouse skin, chronic arsenic exposure through drinking water increases p62 protein levels in the epidermis. Nrf2 is required for basal and arsenic-induced p62 up-regulation. p62 knockdown reduces arsenic-induced Nrf2 activity, and induces sustained p21 up-regulation. p62 induction is associated with increased proliferation in mouse epidermis. p62 knockdown had little effect on arsenic-induced apoptosis, while it decreased cell proliferation following arsenic treatment. Our findings indicate that arsenic induces p62 expression to regulate the Nrf2 pathway in human keratinocytes and suggest that targeting p62 may help prevent arsenic-induced skin cancer.
Source: Molecules
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
Awards: YTHDF2 and UVB damage response in skin cancer, G3306898272, Re-Engineering Translational Research at the University of Chicago, G3894786174, G406168540, Effects of Arsenic on Human Prostate Stem Cells and Prostate Cancer Risk, Mechanisms of UVA-induced skin cancer, G6550811748, G6743951032, G8631870757, G8940433359, G9000074346, G9000334782, Cancer Center Support Grant, ChicAgo Center for Health and EnvironmenT (CACHET)
OpenAlex ID: W2580703485