Yes-Associated Protein 1 Exhibits Oncogenic Property in Gastric Cancer and Its Nuclear Accumulation Associates with Poor Prognosis
Open Access
- 14 April 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 17 (8), 2130-2139
- https://doi.org/10.1158/1078-0432.ccr-10-2467
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
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This publication has 29 references indexed in Scilit:
- Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenograftsNeuro-Oncology, 2009
- Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancerBritish Journal of Cancer, 2009
- Nature meets nurture: molecular genetics of gastric cancerHuman Genetics, 2009
- Yes‐associated protein is an independent prognostic marker in hepatocellular carcinomaCancer, 2009
- Expression of Yes-associated protein in common solid tumorsHuman Pathology, 2008
- Array-CGH identifies cyclin D1 and UBCH10 amplicons in anaplastic thyroid carcinomaEndocrine-Related Cancer, 2008
- TEAD mediates YAP-dependent gene induction and growth controlGenes & Development, 2008
- Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth controlGenes & Development, 2007
- Transforming properties of YAP , a candidate oncogene on the chromosome 11q22 ampliconProceedings of the National Academy of Sciences of the United States of America, 2006
- Identification and Validation of Oncogenes in Liver Cancer Using an Integrative Oncogenomic ApproachCell, 2006