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Xiaowei Xu

Xiaowei Xu

University of Pennsylvania, USA

Title: PHD2 silencing cooperates with BRafV600E to induce melanoma formation

Biography

This lecture will address the role of PHD2, a master oxygen sensor, during melanoma pathogenesis. It will include discussion of: function of PHD2 in cellular response to hypoxia, PHD2 mutations in cancers, the cooperation of PHD2 deletion and BRAF mutation in a mouse model of melanoma. HIF-1α is a key transcription factor involved in the induction of the hypoxia specific gene transcription program. HIF-1alpha protein expression is tightly regulated by oxygen levels. PHD2 regulates the hypoxia induced gene transcription program by controlling the stability of HIF-α through prolyl hydroxylation of the latter. Missense mutations in the human PHD2 gene have been identified in various tumors, including paraganglioma and more recent in melanoma. The function of PHD2 in cancer cells has yet to be fully understood. Our data support a tumor suppressor role of PHD2 in cancer development.

Abstract

This lecture will address the role of PHD2, a master oxygen sensor, during melanoma pathogenesis. It will include discussion of: function of PHD2 in cellular response to hypoxia, PHD2 mutations in cancers, the cooperation of PHD2 deletion and BRAF mutation in a mouse model of melanoma. HIF-1α is a key transcription factor involved in the induction of the hypoxia specific gene transcription program. HIF-1alpha protein expression is tightly regulated by oxygen levels. PHD2 regulates the hypoxia induced gene transcription program by controlling the stability of HIF-α through prolyl hydroxylation of the latter. Missense mutations in the human PHD2 gene have been identified in various tumors, including paraganglioma and more recent in melanoma. The function of PHD2 in cancer cells has yet to be fully understood. Our data support a tumor suppressor role of PHD2 in cancer development.

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