Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies

Haibo Bai, Mariana F. Gayyed, Dora M. Lam-Himlin, Alison P. Klein, Suresh K. Nayar, Yang Xu, Mehtab Khan, Pedram Argani, Duojia Pan, Robert A. Anders

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma account for 95% of primary liver cancer. For each of these malignancies, the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. We observed abnormal proliferation of both biliary epithelium and hepatocytes in mice after genetic manipulation of Yes-associated protein, a transcription coactivator. Here, we comprehensively documented Yes-associated protein expression in the human liver and primary liver cancers. We showed that nuclear Yes-associated protein expression is significantly increased in human intrahepatic cholangiocarcinoma and hepatocellular carcinoma. We found that increased Yes-associated protein levels in hepatocellular carcinoma are due to multiple mechanisms including gene amplification and transcriptional and posttranscriptional regulation. Survivin, a member of the inhibitors-of- apoptosis protein family, has been reported as an independent prognostic factor for poor survival in both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We found that nuclear Yes-associated protein expression correlates significantly with nuclear Survivin expression for both intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Furthermore, using mice engineered to conditionally overexpress Yes-associated protein in the liver, we found that Survivin messenger RNA expression depends upon Yes-associated protein levels. Our findings suggested that Yes-associated protein contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression.

Original languageEnglish (US)
Pages (from-to)1376-1385
Number of pages10
JournalHuman Pathology
Volume43
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Cholangiocarcinoma
  • Hepatocellular carcinoma
  • Survivin
  • Yes-associated protein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Bai, H., Gayyed, M. F., Lam-Himlin, D. M., Klein, A. P., Nayar, S. K., Xu, Y., Khan, M., Argani, P., Pan, D., & Anders, R. A. (2012). Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies. Human Pathology, 43(9), 1376-1385. https://doi.org/10.1016/j.humpath.2011.12.001