Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma

Shuhei Komatsu, Issei Imoto, Hitoshi Tsuda, Ken Ich Kozaki, Tomoki Muramatsu, Yutaka Shimada, Satoshi Aiko, Yutaka Yoshizumi, Daisuke Ichikawa, Eigo Otsuji, Johji Inazawa

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118 Citations (Scopus)

Abstract

Although we have identified two putative targets, ATF3 and CENPF, for a frequently gained/amplified region around 1q32-41 in esophageal squamous cell carcinoma (ESCC), it is possible that other amplification targets remain to be identified. In this study, we tested whether SET and MYND domain-containing protein 2 (SMYD2), located between those two genes and encoding a lysine methyltransferase for histone H3K36 and p53K370 that regulates transcription and inhibits transactivation activity, respectively, acts as a cancer-promoting gene through activation/ overexpression in ESCC. Frequent overexpression of SMYD2 messenger RNA and protein was observed in KYSE150 cells with remarkable amplification at 1q32-41.1 and other ESCC cell lines (11/43 lines, 25.6%). Overexpression of SMYD2 protein was frequently detected in primary tumor samples of ESCC (117/153 cases, 76.5%) as well and significantly correlated with gender, venous invasion, the pT category in the tumor-lymph node-metastases classification and status of recurrence. Patients with SMYD2-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors, and SMYD2 positivity was independently associated with a worse outcome in the multivariate analysis. Knockdown of SMYD2 expression inhibited and ectopic overexpression of SMYD2 promoted the proliferation of ESCC cells in a TP53 mutation-independent but SMYD2 expression-dependent manner. These findings suggest that SMYD2 plays an important role in tumor cell proliferation through its activation/overexpression and highlight its usefulness as a prognosticator and potential therapeutic target in ESCC.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalCarcinogenesis
Volume30
Issue number7
DOIs
Publication statusPublished - Jul 15 2009

ASJC Scopus subject areas

  • Cancer Research

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    Komatsu, S., Imoto, I., Tsuda, H., Kozaki, K. I., Muramatsu, T., Shimada, Y., Aiko, S., Yoshizumi, Y., Ichikawa, D., Otsuji, E., & Inazawa, J. (2009). Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma. Carcinogenesis, 30(7), 1139-1146. https://doi.org/10.1093/carcin/bgp116