YAP is a candidate oncogene for esophageal squamous cell carcinoma

Tomoki Muramatsu, Issei Imoto, Takeshi Matsui, Ken Ichi Kozaki, Shigeo Haruki, Marius Sudol, Yutaka Shimada, Hitoshi Tsuda, Tatsuyuki Kawano, Johji Inazawa

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Abstract

Yes-associated protein (YAP), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene located at chromosome 11q22. Since we previously reported amplification of 11q22 region in esophageal squamous cell carcinoma (ESCC), in this study we focused on the clinical significance and biological functions of YAP in this tumor. Frequent overexpression of YAP protein was observed in ESCC cells including those with a robust amplicon at position 11q22. Overexpression of the YAP protein was frequently detected in primary tumors of ESCC as well. Patients with YAP-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors, and YAP positivity was independently associated with a worse outcome in the multivariate analysis. Further analyses in cells in which YAP was either overexpressed or depleted confirmed that cell proliferation was promoted in a YAP isoform-independent but YAP expression level-dependent manner. YAP depletion inhibited cell proliferation mainly in the G0-G1 phase and induced an increase in CDKN1A/p21 transcription but a decrease in BIRC5/survivin transcription. Our results indicate that YAP is a putative oncogene in ESCC and it represents a potential diagnostic and therapeutic target.

Original languageEnglish
Pages (from-to)389-398
Number of pages10
JournalCarcinogenesis
Volume32
Issue number3
DOIs
Publication statusPublished - Mar 10 2011

ASJC Scopus subject areas

  • Cancer Research

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    Muramatsu, T., Imoto, I., Matsui, T., Kozaki, K. I., Haruki, S., Sudol, M., Shimada, Y., Tsuda, H., Kawano, T., & Inazawa, J. (2011). YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis, 32(3), 389-398. https://doi.org/10.1093/carcin/bgq254