The Involvement of Notch Signaling in Neuroendocrine Prostate Cancer

Date of Award

Spring 2020

Document Type




First Reader

Dr. Blake Johnson

Second Reader

Dr. Nathan Reyna

Third Reader

Dr. Rachel Pool


Neuroendocrine prostate cancer (NEPC) is a more aggressive form of prostate cancer than the one we are most familiar with, prostate adenocarcinoma. In this disease, androgen receptor signaling is lost while the prostate cells are transdifferentiated into neuroendocrine cells. The loss of this androgen signaling results in resistance to androgen-receptor targeted therapies. This distinction makes NEPC a lethal disease that often avoids detection through the routine protocol for discovering prostate cancer. In searching for the next potential target of treatment therapies for NEPC, Notch signaling was identified as a potential answer. Notch signaling has long been suspected to have roles in many aggressive cancers and has been proven to have a connection to the intensity of the disease in ovarian cancer. It could additionally very well have the same effect in neuroendocrine prostate cancer. In this study, we are interested in looking at genes that are correlated with Notch signaling and observing how amplification, deep deletion, or any alteration of those genes might affect the signaling pathway and therefore the intensity of the disease. Both Mgat3 and Mgat5 show a correlation with at least one form of the Notch gene, and therefore could be related to how the disease progresses in the prostate or to the disease intensity or duration. Our initial findings demonstrate that amplification of Mgat3 or Mgat5 do in fact influence the progression of NEPC by significantly changing the Notch signaling pathway, and the mechanism of tumor progression overall.

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