Characterization of regulatory proteins within the Pak2 signaling pathway on prostate cancer migration

Carmona Martinez, Ricardo (2017) Characterization of regulatory proteins within the Pak2 signaling pathway on prostate cancer migration. Masters thesis, Memorial University of Newfoundland.

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Abstract

Prostate cancer is the most frequently diagnosed cancer among men, with an incidence rate of 1 in 7. The mechanisms regulating its abnormal growth and metastasis are not fully understood. Transforming Growth Factor-Beta (TGF-β) has been described as both a negative prognostic indicator and a growth promoter in prostate cancer. The p21-Activated kinase 2 (Pak2) enzyme regulates growth and migration of normal cells and has been shown to be activated by TGF-β. My hypothesis proposes that Pak2 regulates the aberrant migratory properties of prostate cancer. Multiple prostate cancer cell lines, representing multiple stages in disease development were used to define protein and gene expression levels within the Pak2 signaling cascade. P-Merlin levels were used to determine Pak2 activity. There is a shift in the ratio of Pak2 stimulatory proteins with a dominance of CDC42 corresponding with disease progression. The ratio of Merlin to Erbin is altered in all prostate cancer cells. There is an increase in P-Merlin levels corresponding to progression of the disease, indicating an increase in basal Pak2 activity. Pak2 inhibition blocked TGF-β promoted migration in highly metastatic prostate cancer cells PC-3 and DU145. These results demonstrate the Pak2 signaling pathway is not only aberrantly active but that regulates TGF-β induced migration in prostate cancer.

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