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Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-α secretion in gastric cancer

Oncogene volume 33, pages 3918–3926 (2014)Cite this article

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A Correction to this article was published on 07 June 2019

Abstract

We built an in-house oligonucleotide array on which 394 genes were selected based on our Serial Analysis of Gene Expression (SAGE) data and previously reported array data and listed several genes related to cancer progression. Among these, we focused on SEC11A, which encodes the SPC18 protein. SEC11A mRNA expression was measured by quantitative reverse transcription–polymerase chain reaction (qRT–PCR) in gastric cancer (GC) tissue samples. Expression and distribution of SPC18 protein were investigated by immunohistochemical analysis in two independent GC cohorts (Hiroshima cohort, n=99 and Chiba cohort, n=989). To determine the effect of SPC18 on cell viability and invasiveness in vitro, MTT and Boyden chamber invasion assays were performed. To evaluate the influence of SPC18 on cell growth in vivo, GC cells were injected into severe combined immunodeficiency mice. Levels of TGF-α and EGF in media from the GC cells were measured by enzyme-linked immunosorbent assay (ELISA). Studies in human tissue revealed overexpression of SEC11A mRNA in 40% of 42 GC samples by qRT–PCR. Immunohistochemical analysis of SPC18 revealed that 26 and 20% of GC cases were SPC18-positive in the Hiroshima and Chiba cohorts, respectively. In both cohorts, the Kaplan–Meier analysis showed poorer survival in SPC18-positive GC cases than in SPC18-negative GC cases. Forced expression of SPC18 activates GC cell growth in vitro and in vivo. The levels of TGF-α in culture media from GC cells were reduced by knockdown of SPC18. These results indicate that SPC18 contributes to malignant progression through promotion of TGF-α secretion in GC.

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Acknowledgements

We thank Mr Shinichi Norimura for excellent technical assistance and advice. This work was carried out with the kind cooperation of the Research Center for Molecular Medicine, Faculty of Medicine, Hiroshima University. We thank the Analysis Center of Life Science, Hiroshima University, for the use of their facilities.

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Authors and Affiliations

  1. Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

    N Oue, Y Naito, T Hayashi, K Sentani, N Sakamoto, H Zarni Oo, N Uraoka & W Yasui

  2. Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    M Takigahira

  3. Pathology Division, and Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    A Kawano-Nagatsuma & A Ochiai

  4. Division of Translational Research, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    K Yanagihara

  5. Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan

    H Sasaki

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  1. N Oue
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Correspondence to W Yasui.

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Oue, N., Naito, Y., Hayashi, T. et al. Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-α secretion in gastric cancer. Oncogene 33, 3918–3926 (2014). https://doi.org/10.1038/onc.2013.364

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