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Identification and characterization of YAP1 as a functional oncogene in gastric cancer. / CUHK electronic theses & dissertations collection

Array comparative genomic hybridization (array-CGH) was used in this study to analyze the chromosomal aberrations in 9 gastric cancer cell lines. Our results showed good concordance with those of conventional CGH. We correlated the results from array-CGH with expression profiling and found some novel and independent target genes which deserved further confirmation. / Gastric cancer is one of the most common malignancies worldwide and is the second most frequent cause of cancer related death. A variety of genetic and epigenetic aberrations underlie development abnormality of gastric cancer. / Taken together, our findings supported YAP1 is a functional oncogene 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. / The study was focused on the putative oncogene Yes-associated Protein 1 (YAP1) located in 11q22.1. Up-regulation of YAP1 was observed in 92.3% of gastric cancer by immunohistochemistry (IHe) on gastric cancer tissue microarrays. YAP1 nuclear accumulation correlated with cancer specific survival. In addition, multivariate Cox regression showed that YAP1 was an independent predictor of short disease specific survival time for patients with early stage gastric cancer (P=0.042) in addition to T stage ( P=O.038). Knockdown YAP1 in gastric cancer cell lines MKN1 and AGS resulted in a significant reduction in proliferation, anchorage-dependent colony formation, cell invasion and cell motility. Ectopic YAP1 expression in MKN45 cells 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 pathway by YAP1. We confirmed a constitutive activation of RAF/MEKJERK in YAP1-expressing MKN45 cells and further demonstrated that YAP1 enhanced serum/EGF induced c-Fos expression in gastric cancer cells. Furthermore, we demonstrated that ectopic MST1 promoted phosphorylation and cytoplasmic translocation of YAP1 and subsequently quenched the oncogenic function of YAP1 in the nucleus. / Kang, Wei. / "December 2010." / Adviser: To Kai-fai. / Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 175-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344765
Date January 2011
ContributorsKang, Wei, Chinese University of Hong Kong Graduate School. Division of Anatomical & Cellular Pathology.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, theses
Formatelectronic resource, microform, microfiche, 1 online resource (xviii, 185 leaves : ill. (some col.))
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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