Mapping the STK4/Hippo Signaling Network in Prostate Cancer Cell

Ready, Damien, Marquette University
Yagiz, Kader, Cedars-Sinai Medical Center
Amin, Pooneh, Clark Atlanta University
Yildiz, Yuksel, Adnan Menderes University
Funari, Vincent, Cedars-Sinai University
Bozdag, Seardar, Marquette University
Cinar, Bekir, Clark Atlanta University

2017-09-07

2010-2019

Dysregulation of MST1/STK4, a key kinase component of the Hippo-YAP pathway, is linked to the etiology of many cancers with poor prognosis. However, how STK4 restricts the emergence of aggressive cancer remains elusive. Here, we investigated the effects of STK4, primarily localized in the cytoplasm, lipid raft, and nucleus, on cell growth and gene expression in aggressive prostate cancer. We demonstrated that lipid raft and nuclear STK4 had superior suppressive effects on cell growth in vitro and in vivo compared with cytoplasmic STK4. Using RNA sequencing and bioinformatics analysis, we identified several differentially expressed (DE) genes that responded to ectopic STK4 in all three subcellular compartments. We noted that the number of DE genes observed in lipid raft and nuclear STK4 cells were much greater than cytoplasmic STK4. Our functional annotation clustering showed that these DE genes were commonly associated with oncogenic pathways such as AR, PI3K/AKT, BMP/SMAD, GPCR, WNT, and RAS as well as unique pathways such as JAK/STAT, which emerged only in nuclear STK4 cells. These findings indicate that MST1/STK4/Hippo signaling restricts aggressive tumor cell growth by intersecting with multiple molecular pathways, suggesting that targeting of the STK4/Hippo pathway may have important therapeutic implications for cancer.

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PLOS One

Clark Atlanta University

10.1371/journal.pone.0184590

http://hdl.handle.net/20.500.12322/cau.ir:2017_cinar_2

http://rightsstatements.org/vocab/InC/1.0/