Stathmin: A Relay Protein in the Development of Prostate Cancer and a Potential Target for Anti-Cancer Therapy
Abstract
The long term goal of this work is to determine whether stathmin can be targeted as an effective therapy in the clinic against prostate cancer (PCa). The purpose of this work is to i)correlate stathmin overexpression with progression of PCa ii) determine the signaling pathways activated through selective phosphorylation of stathmin and whether inactivation of these pathways promotes sensitization to treatment with Taxotere or Erbitux iii)examine the effects of stathmin expression on tumor development and the outcomes of Taxotere Erbitux on blocking tumorigenesis in tissue recombination and and transgenic mouse models. We have identified that stathmin modulates TGFbeta signaling in inducing epithelial-to-mesenchymal transformation of PCa cells. We have also established for the first time that p38MAPK acts downstream of stathmin in this pathway. Loss of stathmin results in the sequestering of phosphorylated Smad in the cellular cytoplasm. In its place the Smad-independent MAPKpathway is activated as seen by p38 phosphorylation and the appearance of spindle-shaped cells. Thus we have identified stathmin as a major regulator of epithelial cell homeostasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2007
- Accession Number
- ADA477292
Entities
People
- Ritwik Ghosh
Organizations
- Vanderbilt University Medical Center