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Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer

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Abstract

Abnormalities in signal transducer and activator of transcription (STAT) signaling, especially STAT3 and STAT5, are involved in the oncogenesis of several human cancers, including gastric cancer (GC). However, the downstream targets of STAT3 and STAT5 are not fully identified, and the precise roles and the prognostic value of STAT3 and STAT5 in GC have not been fully characterized. In this study, we used ChIP-on-chip to identify STAT3 and STAT5 target genes on a whole genome scale in AGS cells, a human GC cell line. A total of 2,514 and 1,314 genes were identified as STAT3 and STAT5 target genes, which were mainly related to cell growth, metabolism, differentiation, adhesion, immune response, and stress response. Furthermore, we depleted STAT3 and STAT5 with a small interfering RNA, respectively. Our results demonstrate that STAT3, but not STAT5, is involved in GC cell growth and cell cycle progression through regulation of gene expression, such as Bcl-2, p16ink4a and p21waf1/cip1. Moreover, expression of pSTAT3Tyr705 correlates with TNM stage, differentiation and survival, and is a significant prognostic factor in GC. Therefore, our findings provide novel evidence that STAT3 may be a potential therapeutic target for GC treatment and pSTAT3Tyr705 expression can predict prognosis in GC.

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Acknowledgments

This work was supported by the National Basic Research Program of China 973 program Grant (no. 2010CB5293), National Nature Science Foundation of China (NSFC, no. 30830055), grants from NSFC (no. 30900757) and Shanghai Rising-Star Program (no. 10QA1404400). The funding had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Special thanks go to Genminix Company for excellent technical assistance in microarray result analysis.

Conflict of interest

The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Shanghai, China

    Hua Xiong, Wan Du, Ji-Lin Wang, Ying-Chao Wang, Jie-Ting Tang, Jie Hong & Jing-Yuan Fang

  2. Key Laboratory of Gastroenterology and Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China

    Hua Xiong, Wan Du, Ji-Lin Wang, Ying-Chao Wang, Jie-Ting Tang, Jie Hong & Jing-Yuan Fang

  3. State Key Laboratory of Oncogene and Related Genes, 145 Middle Shandong Rd, Shanghai, 200001, China

    Hua Xiong, Wan Du, Ji-Lin Wang, Ying-Chao Wang, Jie-Ting Tang, Jie Hong & Jing-Yuan Fang

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  1. Hua Xiong
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  2. Wan Du
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  3. Ji-Lin Wang
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  5. Jie-Ting Tang
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Correspondence to Jing-Yuan Fang.

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ESM 1

The potential STAT3 and STAT5 target genes from the ChIP-on-chip in AGS cells. The ratio value (column E, blue part) of every gene was calculated by cutting off the value in control antibody group. A total of 2,514 and 1,314 genes were identified as STAT3 and STAT5 target genes, by setting the filter for ratio values of ≥2.0. (PDF 1266 kb)

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Xiong, H., Du, W., Wang, JL. et al. Constitutive activation of STAT3 is predictive of poor prognosis in human gastric cancer. J Mol Med 90, 1037–1046 (2012). https://doi.org/10.1007/s00109-012-0869-0

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  • DOI: https://doi.org/10.1007/s00109-012-0869-0

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