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2016 ; 7
(51
): 84634-84644
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gab.com Text
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Unraveling the expression of the oncogene YAP1, a Wnt/beta-catenin target, in
adrenocortical tumors and its association with poor outcome in pediatric
patients
#MMPMID27705928
Abduch RH
; Carolina Bueno A
; Leal LF
; Cavalcanti MM
; Gomes DC
; Brandalise SR
; Masterallo MJ
; Yunes JA
; Martinelli CE Jr
; Tone LG
; Tucci S
; Molina CA
; Ramalho FS
; Moreira AC
; Cardinalli IA
; Scrideli CA
; Ramalho LN
; de Castro M
; Antonini SR
Oncotarget
2016[Dec]; 7
(51
): 84634-84644
PMID27705928
show ga
BACKGROUND: Overexpression of the oncogene yes-associated-protein-1 (YAP1) is
associated with increased cell proliferation in human cancers. YAP1 is a
potential target of the Wnt/beta-catenin pathway, which plays an important role
in adrenocortical tumors (ACT). The role of YAP1 in adrenocortical tumorigenesis
has not been assessed. AIMS: To evaluate YAP1 expression in normal adrenals and
pediatric ACT and its association with disease outcome. To investigate the
interaction between YAP1 and the Wnt/beta-catenin pathway in adrenocortical
cells. RESULTS: Strong YAP1 staining was present in fetal adrenals and pediatric
ACT but weak in postnatal adrenals. In pediatric ACT, YAP1 mRNA overexpression
was associated with death, recurrent/metastatic disease and lower overall
survival. The inhibition of the Wnt/beta-catenin pathway increased YAP1 mRNA
expression. siYAP1 increased CTNNB1/beta-catenin expression and nuclear staining
regardless of DLV2, moreover, it decreased cell growth and impaired cell
migration. MATERIALS AND METHODS: We assessed in 42 pediatric ACT samples the
YAP1 protein expression by immunohistochemistry and mRNA expression by RT-qPCR
and analyzed their association with outcome. As controls, we resort 32 fetal and
postnatal normal adrenals for IHC and 10 normal adrenal cortices for RT-qPCR. The
interaction between YAP1 and the Wnt/beta-catenin pathway was assessed in
NCI-H295 adrenocortical cells by inhibiting the TCF/beta-catenin complex and by
knocking down YAP1. CONCLUSION: YAP1 overexpression is a marker of poor prognosis
for pediatric patients with ACT. In adrenocortical cells, there is a close
crosstalk between YAP1 and Wnt/beta-catenin. These data open the possibility of
future molecular therapies targeting Hippo/YAP1 signaling to treat advanced ACT.
|Adaptor Proteins, Signal Transducing/genetics/*metabolism
[MESH]