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Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation

  • Ruan, Banzhan (School of Biology and Biological Engineering, South China University of Technology) ;
  • Wang, Chenxi (School of Biology and Biological Engineering, South China University of Technology) ;
  • Chen, Ang (Laboratory of Cell Engineering, Institute of Biotechnology) ;
  • Liang, Jianqing (School of Biology and Biological Engineering, South China University of Technology) ;
  • Niu, Zubiao (Laboratory of Cell Engineering, Institute of Biotechnology) ;
  • Zheng, You (Laboratory of Cell Engineering, Institute of Biotechnology) ;
  • Fan, Jie (Laboratory of Cell Engineering, Institute of Biotechnology) ;
  • Gao, Lihua (Laboratory of Cell Engineering, Institute of Biotechnology) ;
  • Huang, Hongyan (Department of Oncology, Beijing Shijitan Hospital of Capital Medical University) ;
  • Wang, Xiaoning (School of Biology and Biological Engineering, South China University of Technology) ;
  • Sun, Qiang (Laboratory of Cell Engineering, Institute of Biotechnology)
  • Received : 2018.04.22
  • Accepted : 2018.07.02
  • Published : 2018.08.31

Abstract

Homotypic cell-in-cell (CIC) structures forming between cancer cells were proposed to promote tumor evolution via entosis, a nonapoptotic cell death process. However, the mechanisms underlying their formation remained poorly understood. We performed a microarray analysis to identify genes associated with homotypic CIC formation. Cancer cells differing in their ability to form homotypic CIC structures were selected for the study. Association analysis identified 73 probe sets for 62 candidate genes potentially involved in CIC formation. Among them, twenty-one genes were downregulated while 41 genes were upregulated. Pathway analysis identified a gene interaction network centered on IL-8, which was upregulated in high CIC cells. Remarkably, CIC formation was significantly inhibited by IL-8 knockdown and enhanced upon recombinant IL-8 treatment, which correlated with altered cell-cell adhesion and expression of adhesive molecules such as P-cadherin and ${\gamma}$-catenin. Together, our work identified IL-8 as a positive regulator of homotypic CIC formation via enhancing intercellular adhesion.

Keywords

References

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Cited by

  1. Cell-in-cell phenomena in cancer vol.18, pp.12, 2018, https://doi.org/10.1038/s41568-018-0073-9