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Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression

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Tumor Biology

Abstract

Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1 expression using specific small interfering RNAs in butyrate-treated SK-MEL-5 cells resulted in increased expression of the epithelial marker E-cadherin and decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression of the E-cadherin. Collectively, these results indicate that butyrate induces the expression of ANXA1 in human melanoma cells, which then promotes invasion through activating the EMT signaling pathway.

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Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2013R1A1A2008633) and Asan Institute for Life Sciences, Seoul, Korea (2014-570).

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 138-736, South Korea

    Jimin Shin, In-Sung Song & Sung-Wuk Jang

  2. Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 138-736, South Korea

    Jimin Shin, In-Sung Song & Sung-Wuk Jang

  3. Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, South Korea

    Jimin Shin, In-Sung Song & Jhang Ho Pak

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  1. Jimin Shin
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  2. In-Sung Song
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Correspondence to Sung-Wuk Jang.

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Jimin Shin and In-Sung Song contributed equally to this work.

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Shin, J., Song, IS., Pak, J.H. et al. Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression. Tumor Biol. 37, 14577–14584 (2016). https://doi.org/10.1007/s13277-016-5306-5

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  • DOI: https://doi.org/10.1007/s13277-016-5306-5

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