Date of Award

5-4-2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Zhi-Ren Liu

Abstract

P68 RNA helicase, a prototypical member of the DEAD box family of RNA helicases is important in many biological processes, including early organ development. However, its aberrant expression contributes to tumor development and progression. In this study, we show that p68 upregulates the transcriptional expression of the growth factor receptor, PDGFRb P68 knockdown in MDAMB231 and BT549 breast cancer cells significantly decreases mRNA and protein levels of PDGFRb and EMT markers, resulting in decreased migration. We have previously shown that PDGF-BB induces p68 phosphorylation, resulting in EMT via nuclear translocation of b -catenin. Here, we show that p68 promotes migration in response to PDGF-BB stimulation via upregulation of PDGFRb in breast cancer cells, suggesting that PDGFRb is in turn regulated by p68 to maintain a positive feedback loop. Further, our study reveals the association of p68 in androgen receptor (AR) response via PDGFRb. We demonstrate that p68 and PDGFRb co-regulate AR expression and promote androgen-mediated proliferation in breast cancer cells, highlighting the critical role of p68-PDGFRb axis in AR regulation

DOI

https://doi.org/10.57709/17547775

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