Therapeutic Value of PLK1 Knockdown in Combination with Prostate Cancer Drugs in PIM-1 Overexpressing Prostate Cancer Cells
Abstract
The treatment options for advanced prostate cancer are limited, thus intensive efforts are ongoing to explore novel targets and strategies for the management of prostate cancer. Our ultimate goal is to identify new target that can specifically sensitize Pim-1 overexpressing prostate cancer cells. Pim-1 is highly overexpressed in prostate cancer and overexpression of Pim-1 leads to genomic instability and docetaxel resistance in prostate epithelial cells. PIM1 synergizes with c-MYC to induce advanced prostate cancer in a kinase-dependent manner. Using a siRNA library screen, we identified Polo-like kinase (PLK1) as a promising target whose knockdown can specifically reduce the cell viability of Pim-1 overexpressing cells. PLK1 is also overexpressed in a wide variety of cancer types including prostate and its expression frequently correlates with poor patient prognosis. PLK1 has been an attractive molecular target for cancer therapy due to its structural hallmarks, its overexpression in various cancer types, and the intrinsic dependence of tumor cells on its activity in mitosis. Silencing of PLK1 has been shown to enhance drug sensitivity in some cancer cells such as pancreatic adenocarcinoma and breast. Our main goal is to test whether depletion of PLK1 will result in synthetic lethality in Pim-1 overexpressing cells and whether depletion of PLK1 will further sensitize Pim-1 overexpressing cells to prostate cancer drugs.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2012
- Accession Number
- ADA562177
Entities
People
- Meejeon Roh
Organizations
- Vanderbilt University