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Publications of the Week

Non-Canonical Activation of Hedgehog in Prostate Cancer Cells Mediated by the Interaction of Transcriptionally Active Androgen Receptor Proteins with Gli3

By February 28, 2018No Comments

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 This week we profile a recent publication in Science Translational Medicine from the lab of
Dr. Ralph Buttyan (second from left, front) at the Vancouver Prostate Centre

Can you provide a brief overview of your lab’s current research focus?

Prostate cancer remains a leading cause of cancer deaths in men. These deaths are associated with the “castration-resistant” form of the disease that develops subsequent to hormone therapies used when patients present with metastasis. The Buttyan lab is focused on developing an understanding of progression to castration-resistant disease and on using this understanding to develop new therapeutics to more effectively treat men with metastatic prostate cancer.

What is the significance of the findings in this publication?

Hedgehog is a cell signalling pathway needed for normal embryonic development.  Hyperactive Hedgehog in adult tissues, however, is oncogenic and is causative of skin and brain cancers. Though Hedgehog has long been thought to be a factor in prostate cancer, the means of its activation were unclear. A recent publication from the Buttyan lab at the Vancouver Prostate Centre has shown that Hedgehog is activated in prostate cancer by the direct interaction of androgen receptor proteins with Gli, the transcription factor that is the target of Hedgehog signalling. This interaction protects Gli from degradation, maintaining it in an active form. Thus the androgen receptor bypasses the upstream controls on Gli and mimics a hyperactive Hedgehog signalling state. As Gli controls genes that regulate cell growth, this relationship suggests that Gli activation may be important for the abnormal growth of prostate cancer cells.

What are the next steps for this research?

We are currently exploring the relationship between Gli and prostate cancer cell growth and focused on determining the nature of the Gli transcriptome in prostate cancer cells.

This project was supported by:

CIHR, Prostate Cancer Canada-Movember Team Grant T2013, Terry Fox Research Institute New Frontiers Program PPG 1062

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