Expression of Yes-associated protein in gastric adenocarcinoma and inhibitory effects of its knockdown on gastric cancer cell proliferation and metastasis

Int J Immunopathol Pharmacol. 2012 Jul-Sep;25(3):583-90. doi: 10.1177/039463201202500304.

Abstract

Yes-associated protein (YAP) has been implicated as an oncogene in multiple human cancers. In the present study, human gastric adenocarcinoma tissues of different grades (N=78) were collected and the mRNA and protein expression of YAP and phosphorylated YAP (p-YAP) in gastric adenocarcinomas were evaluated using immunohistochemistry, Real-time PCR and Western blot assays. Then, human gastric cancer SGC-7901 cells were stably transfected with lentivirus-mediated YAP small hairpin RNA (shRNA). The expression levels of YAP, proliferating cell nuclear antigen (PCNA) and metalloproteinase-2 (MMP-2) were detected and the effects of shRNA-mediated knockdown of YAP on cell proliferation and metastasis were assessed in gastric cancer cells. As a result, the expression of YAP was observed in 69.23 percent gastric adenocarcinoma tissues, elevating with the ascending order of tumor malignancy. Knockdown of YAP could down-regulated the expression of PCNA and MMP-2, and inhibit the proliferation and metastasis of gastric cancer cells. In conclusion, YAP is strongly expressed in gastric adenocarcinomas, and knockdown of YAP may inhibit gastric cancer cell proliferation and metastasis through down-regulation of PCNA and MMP-2 expression, suggesting that YAP represents an important therapeutic target in human gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Gene Knockdown Techniques*
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / metabolism
  • Neoplasm Invasiveness
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Nuclear Proteins
  • Phosphoproteins
  • Proliferating Cell Nuclear Antigen
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • MMP2 protein, human
  • Matrix Metalloproteinase 2