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Enteropathogenic Escherichia coli-induced macrophage inhibitory cytokine 1 mediates cancer cell survival: an in vitro implication of infection-linked tumor dissemination

Oncogene volume 32, pages 4960–4969 (2013)Cite this article

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Abstract

Mucosally adherent Escherichia coli is frequently observed in intestinal surface of patients with colorectal cancer, but rarely in healthy control. Particularly, enteropathogenic Escherichia coli (EPEC) is known to be closely associated with colorectal carcinogenesis in human. In this study, one consequence of EPEC infection in human intestinal cancer cells was induction of macrophage inhibitory cytokine 1 (MIC-1), which is a multifunctional cytokine with biological activities involved in cancer cell growth, differentiation and migration. The present investigation assessed the involvement of MIC-1 protein in EPEC infection-mediated cancer cell survival. The challenge with EPEC induced cancer cell detachment via cytoskeleton rearrangement, which was positively associated with induced MIC-1 expression. Moreover, MIC-1 also mediated RhoA GTPase-linked survival of the detached cancer cells. Blocking of MIC-1 or RhoA activity increased cellular apoptosis of the detached cancer cells. In terms of signaling pathway, MIC-1 triggered transforming growth factorβ-activated kinase 1 (TAK1), which enhanced expression of RhoA GTPase. We conclude that EPEC enhances MIC-1 gene expression in the human intestinal cancer cells, which can be associated with enhanced tumor cell resistance to anchorage-dependent tumor cell death via enhanced TAK1 and RhoA GTPase.

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Acknowledgements

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea, funded by Ministry of Education, Science and Technology Grant 2012R1A1A2005837.

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Authors and Affiliations

  1. Department of Microbiology and Immunology and Medical Research Institute, Laboratory of Mucosal Exposome and Biomodulation, Pusan National University School of Medicine, Yangsan, Kyungnam, Korea,

    H J Choi, J Kim, K H Do, S-H Park & Y Moon

  2. Research Institute for Basic Sciences and Medical Research Institute, Pusan National University, Busan, Korea

    Y Moon

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Choi, H., Kim, J., Do, K. et al. Enteropathogenic Escherichia coli-induced macrophage inhibitory cytokine 1 mediates cancer cell survival: an in vitro implication of infection-linked tumor dissemination. Oncogene 32, 4960–4969 (2013). https://doi.org/10.1038/onc.2012.508

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