Date of Award

Summer 2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Bioinformatics

First Advisor

Bozdag, Serdar

Second Advisor

Clough, Anne

Third Advisor

Cinar, Bekir

Abstract

The SKT4-encoded MST1 is a serine-threonine protein kinase and has known associations with many diseases and cancer.MST1 plays a critical component of the Hippo tumor suppressor pathway responsible for limiting cell division and promoting apoptosis.Loss of MST1 function is associated with poor prognostic outcomes for cancers, though the mechanism is not well understood.There is increasing evidence that dysregulation of MST1 can lead to castration-resistant prostate cancer (CRPCa), an aggressive cancer with limited treatment options.To better understand the mechanistic underpinnings of CRPCa progression, C4-2 prostate cancer cells were engineered toexpress MST1 protein directed to a particular subcellular region: membrane, nucleus, or cytoplasm.Localized MST1 expression resulted in a marked impact to cell growth in vitroand in vivo, which was further characterized by performing whole transcriptome profiling using RNA-Sequencing.Multiple genes were identified with altered expression patterns, which could influence future mechanistic studies of CRPCa progression.

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