Heemers Lab Discovers Novel Mechanism that Drives Prostate Cancer

Research from the laboratory of Hannelore Heemers, PhD, Department of Cancer Biology in the Lerner Research Institute, uncovered a previously unknown driver of prostate cancer which may be a viable target for treatment. The findings were published in the high-impact journal e-Life.

Male hormones called androgens are necessary for the survival and proliferation of prostate cancer cells. When androgens bind to their receptor in prostate cancer cells, the receptor activates and sets into motion a complex cascade of cellular signals that promote cancer growth. Currently, standard treatment for prostate cancer involves blocking androgens from binding to their receptor altogether. While this is successful in early stages, prostate cancer cells eventually become resistant and continue to metastasize, or spread.

Rather than focus on preventing the androgen receptor from becoming activated, Dr. Heemers' team set out to determine where the receptor activity might be blocked after activation. They screened a panel of 18 coregulator proteins known to be involved with the androgen receptor to determine which ones might be driving prostate cancer. Coregulators are proteins that interact with other molecules to either activate or repress gene expression.

The team identified the WDR77 coregulator protein as a key player in prostate cancer progression. When recruited to the androgen receptor, WDR77 fosters a previously unknown interaction with p53, and this interaction regulates expression of genes that control growth of prostate cancer cells. Normally p53 prevents metastasis by destroying unnecessary and harmful cells.

This finding provides strong evidence that targeting the interactions between androgen receptor and WDR77 or other post-receptor coregulators may be beneficial in treating prostate cancer that has become resistant to standard treatment and should be further explored.

Song Liu, PhD, of the Roswell Park Cancer Institute, and Sangeeta Kumari, PhD, of the Lerner Research Institute, are first authors on the publication. Dr. Heemers is a member of the Prostate Cancer Center of Excellence at Cleveland Clinic.