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2017 ; 10
(ä): 2931-2942
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WWC3 downregulation correlates with poor prognosis and inhibition of Hippo
signaling in human gastric cancer
#MMPMID28652775
Hou J
; Zhou J
Onco Targets Ther
2017[]; 10
(ä): 2931-2942
PMID28652775
show ga
The aim of this study was to investigate the clinicopathological significance and
biological roles of WWC3 in human gastric cancer (GC). Clinical significance of
WWC3 in human GCs was examined by using immunohistochemistry (IHC). WWC3 was
downregulated in 48 of 111 human GCs, and its downregulation was associated with
advanced stage, positive nodal status, and higher relapse rate. Importantly, WWC3
downregulation correlated with poor survival. It was also found that WWC3 protein
expression was downregulated in GC cell lines compared with normal cell line
GES-1. On one hand, WWC3 overexpression inhibited the cell growth rate and
invading ability in HGC-27 cell line. On the other hand, depleting WWC3 by small
interfering RNA (siRNA) promoted proliferation rate and invading ability in the
SGC-7901 cell line. In addition, cell cycle analysis showed that WWC3
overexpression inhibited while its depletion accelerated cell cycle progression
at the G1/S transition. Western blot (WB) analysis demonstrated that WWC3
repressed cyclin D1 and cyclin E while upregulated p27 expression. Luciferase
reporter assay showed that WWC3 activated Hippo signaling pathway by suppressing
TEAD transcription activity, with downregulation of total and nuclear YAP and its
target CTGF. WWC3 siRNA depletion exhibited the opposite effects. In conclusion,
this study indicates that WWC3 serves as a tumor suppressor in GC by activating
Hippo signaling.