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Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

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Technical Report,31 Aug 2015,30 Aug 2016

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Columbia University New York United States

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Radiotherapy is a common therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to proliferate under genotoxic stress. The goal of this project is to determine whether silencing of MEK5 will sensitize prostate cancer cells to ionizing radiation. Mitogen-activated protein kinase kinase 5 MAP2K5MEK5 is a member of the MAPK family of protein kinases. MEK5 is often overexpressed in human prostate tumors and it is involved in tumor initiation and progression. In the current funding period we have been able to show that treatment of prostate cancer cells with ionizing radiation leads to activation of ERK5, which is the sole downstream effector of MEK5, whereas depletion of MEK5 sensitizes prostate cancer cells to -radiation as determined by both clonogenic survival and cell proliferation assays. Furthermore, MEK5 silencing impacts on the activation of key modulators of the DNA damage response pathway. In addition, Akt activation in response to ionizing radiation is reduced by MEK5 downregulation. Altogether, these findings suggest that MEK5 could be targeted for therapeutic purposes in prostate cancer patients treated with ionizing radiation.

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