Stathmin Phosphorylation as a Target for Blocking Metastasis in Prostate Cancer
Technical Report,30 Sep 2018,29 Sep 2019
University of Cincinnati Cincinnati United States
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Metastasis is a primary cause of cancer-related deaths, yet this process remains poorly understood. Stathmin Stmn1 is an oncoprotein over-expressed in many cancers, including prostate cancer PCa. While increased Stmn1 correlates with disease progression and poor prognostic outcome, however its role in metastasis is still being elucidated. Stmn1 activity is controlled by four serines S16, S25, S38, and S63 which are differential phosphorylation by 4 different pathways. Therefore the purpose of this study is to determine which one of these serines and associated pathway regulates proliferation and which promotes metastasis. The hypothesis is that the first serine, S16, is the predominant serine that regulates PCa cell proliferation and acts as a gatekeeper to inhibit a cascade leading to metastatic PCa. To address this hypothesis, Specific Aim 1 will determine the function of Stmn1 S16 and the inter-relationship between S16, S25, S38 andor S63 phosphorylation in regulating cell proliferation and a malignant phenotype, Specific Aim 2 will determine the impact of Stmn1 phosphorylation on metastasis using a zebrafish xenograft model and Specific Aim 3 will determine the clinical relevance of the different phospho-Stmn1s by analyzing human Tissue Microarrays representing the range of prostate cancer progression from benign to metastatic cancer. This approach will identify the major Stmn1 phospho-forms expressed during the different stages of prostate cancer progression and determine whether a specific isoform could serve as a biomarker for prostate cancer progression.
- Medicine and Medical Research