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Data from Yes-Associated Protein 1 Exhibits Oncogenic Property in Gastric Cancer and Its Nuclear Accumulation Associates with Poor Prognosis
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Data from Yes-Associated Protein 1 Exhibits Oncogenic Property in Gastric Cancer and Its Nuclear Accumulation Associates with Poor Prognosis
Data from Yes-Associated Protein 1 Exhibits Oncogenic Property in Gastric Cancer and Its Nuclear Accumulation Associates with Poor Prognosis
WK
Wei Kang
Wei Kang
JT
Joanna H.M. Tong
Joanna H.M. Tong
AC
Anthony W.H. Chan
Anthony W.H. Chan
TL
Tin-Lap Lee
Tin-Lap Lee
RL
Raymond W.M. Lung
Raymond W.M. Lung
PL
Patrick P.S. Leung
Patrick P.S. Leung
KS
Ken K.Y. So
Ken K.Y. So
KW
Kaichun Wu
Kaichun Wu
DF
Daiming Fan
Daiming Fan
JY
Jun Yu
Jun Yu
JS
Joseph J.Y. Sung
Joseph J.Y. Sung
KT
Ka-Fai To
Ka-Fai To
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31 March 2023
other
Published by
American Association for Cancer Research (AACR)
https://doi.org/10.1158/1078-0432.c.6519390
Abstract
Purpose: Yes-associated protein 1 (YAP1) is a multifunctional protein that can interact with different transcription factors to activate gene expression. The role of YAP1 in tumorigenesis is unclear. We aimed to investigate the functional role of YAP1 in tumorigenesis of gastric cancer.Experimental Design: YAP1 expresson in gastric adenocarcinoma was evaluated. The biological function was determined by proliferation assay, colony formation, cell invasion, and flow cytometric analysis through knocking down or ectopic expressing YAP1 in gastric cancer cell lines coupled with in vivo study. The possible downstream effectors of YAP1 were investigated by expression microarray.Results: YAP1 protein expression was upregulated in gastric cancer. Nuclear accumulation of YAP1 was associated with poor disease-specific survival (P = 0.021), especially in patients with early-stage diseases (P < 0.001). Knockdown YAP1 resulted in a significant reduction in proliferation, anchorage-dependent colony formation, cell invasion, and cell motility. Ectopic YAP1 expression promoted anchorage-independent colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Microarray analysis highlighted the alteration of MAPK (mitogen-activated protein kinase) pathway by YAP1. We confirmed a constitutive activation of RAF/MEK/ERK (extracellular signal-regulated kinase) in YAP1-expressing MKN45 cells and further showed that YAP1 enhanced serum/epidermal growth factor–induced c-Fos expression in gastric cancer cells.Conclusions: Our findings supported that YAP1 exhibits oncogenic property in gastric cancer. We provided the first evidence that YAP1 exerted the oncogenic function by enhancing the capacity to activate the early-response gene pathway. YAP1 could be a prognostic biomarker and potential therapeutic target for gastric cancer. Clin Cancer Res; 17(8); 2130–9. ©2011 AACR.
Keywords
PROTEIN
FUNCTION
GENE EXPRESSION
TRANSCRIPTION FACTORS
YAP1
EXHIBITS ONCOGENIC PROPERTY
PROPERTY IN GASTRIC
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Open Access