Investigating the Role of PCM1 and Mib1 in Regulating Ciliogenesis and in Prostate Cancer
Abstract
The purpose of this research is to reveal the relationship between assembly of the primary cilium and prostate cancer by investigating two centrosomal proteins, pericentriolar material 1 (PCM1) and Mind bomb 1 (Mib1), and to test the possibility that these proteins can serve as robust prostate cancer biomarkers and,potentially, targets for drug discovery. The primary cilium serves as a cellular antenna, and this organelle inhibits cell proliferation. The loss of this key signaling organelle was reported in various cancers, including prostate cancer. Therefore, we hypothesize that the absence of a primary cilium can potentially trigger cellproliferation and prostate cancer development. Pericentiolar material 1 is essential for ciliogenesis, and the PCM1 gene is deleted in ~15% of prostate cancers. Our results indicate that ablation of pericentriolar material 1 leads to aberrant expression of its interacting partner, Mind bomb 1, an enzyme that is a negative regulator of ciliogenesis. Based on these data, we hypothesize that elevated levels of Mind bomb1 provoked by pericentriolar material 1 depletion in prostate cancer promote abnormal cell growth and malignancy by preventing the assembly of cilia. To test this hypothesis, we will investigate the impact of pericentriolar material 1 deletions in prostate cancer and determine whether there is a correlation between increased Mind bomb 1, the loss of cilia, and the stage of prostate tumor progression. Next, we will test whether pericentriolar material 1 depletion and aberrant levels of Mind bomb 1 promote prostate cancer development. Finally, we will investigate whether Mind bomb 1 removal induces ciliogenesis and inhibits growth of prostate cancer to determine the suitability of Mind bomb 1 as a target of anti-cancer drugs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2017
- Accession Number
- AD1050228
Entities
People
- Lei Wang
Organizations
- New York University