A comprehensive evaluation of Hippo pathway silencing in sarcomas

Oncotarget
Nicole M MerrittMunir R Tanas

Abstract

TAZ and YAP are transcriptional coactivators negatively regulated by the Hippo pathway that have emerged as key oncoproteins in several cancers including sarcomas. We hypothesized that loss of expression of the Hippo kinases might be a mechanism of activating TAZ and YAP. By immunohistochemistry, TAZ/YAP activated clinical sarcoma samples demonstrated loss of MST1 (47%), MST2 (26%), LATS1 (19%), and LATS2 (27%). Western blot similarly demonstrated loss of MST1 (58%), MST2 (25%), and LATS2 (17%). Treatment with MG132 demonstrated an accumulation of MST2 in 25% of sarcoma cell lines, indicating that proteosomal degradation regulates MST2 expression. qRT-PCR in sarcoma cell lines demonstrated loss of expression of the Hippo kinases at the RNA level, most pronounced in MST1 (42%) and MST2 (25%). 5-azacytidine treatment in sarcoma cell lines modestly reversed expression of predominantly MST1 (8%) and MST2 (17%), indicating CpG island hypermethylation can silence expression of MST1 and MST2. Trichostatin A treatment reversed expression of MST1 (58%) and MST2 (67%), indicating histone deacetylation also plays a role in silencing expression of MST1 and MST2. Loss of expression of the Hippo kinases is frequent in sarcomas and is due to ...Continue Reading

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Citations

Sep 4, 2019·Molecular Carcinogenesis·Changbao ChenXinlong Ma
Dec 11, 2019·DNA and Cell Biology·Cong ZhangXiaotao Wu
Jun 20, 2020·Nature Reviews. Drug Discovery·Anwesha DeyKun-Liang Guan
Jul 1, 2021·Signal Transduction and Targeted Therapy·Victoria DamerellSharon Prince

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Methods Mentioned

BETA
Fluorescence
histone acetylation
Protein Assay
PCR

Software Mentioned

Photoshop
cellSens
Image J
SPOT
CytoVision

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