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- W1156918879 abstract "Non-melanoma skin cancers, the most common cancers in the United States, result from chronic exposure to ultraviolet irradiation (UV). UV-induced DNA damage activates cell cycle checkpoints through a mechanism involving degradation of the cyclin dependent kinase activators, the cell division cycle 25 (CDC25) phosphatases, and also activates Erbb family members indirectly through reactive oxygen species (ROS)-inhibition of tyrosine phosphatases to stimulate proliferation. CDC25 family members, including CDC25A, CDC25B and CDC25C, are over-expressed in many human cancers, often correlating with poor prognosis. In this research, the hypothesis that Erbb2 up-regulation of CDC25 phosphatases increases cell proliferation and contributes to skin cancer development was evaluated. CDC25A and CDC25C, but not CDC25B, expression were increased in the cytoplasm of both human and UV-induced mouse skin cancers. Mouse skin tumor experiments with Erbb2 inhibition or genetic deletion of Erbb2 in keratinocytes in culture demonstrated that increased CDC25A and CDC25C expression in squamous cell carcinoma (SCC) were dependent on Erbb2 signaling. Surprisingly, CDC25A and CDC25C did not stimulate proliferation in human SCC cells, but rather suppressed apoptosis. CDC25A-mediated suppression of apoptosis was dependent on its cytoplasmic localization and on interaction with 14-3-3e and Apoptosis Signaling Kinase 1 (ASK1). In contrast, CDC25C did not require 14-3-3 binding or cytoplasmic localization to suppress apoptosis, but rather resulted in inhibitory phosphorylation of pro-apoptotic BAD and elevation of the anti-apoptotic survivin. These data suggest that targeting CDC25A and CDC25C may be a strategy for therapeutic intervention in skin cancer." @default.
- W1156918879 created "2016-06-24" @default.
- W1156918879 creator A5044198115 @default.
- W1156918879 date "2014-06-19" @default.
- W1156918879 modified "2023-09-27" @default.
- W1156918879 title "Role of CDC25 Phosphatases in Non-Melanoma Skin Cancer" @default.
- W1156918879 hasPublicationYear "2014" @default.
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