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Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation
Banzhan Ruan1,2,*,#, Chenxi Wang1,2,#, Ang Chen2, Jianqing Liang1,2, Zubiao Niu2, You Zheng2,6, Jie Fan2,3, Lihua Gao2, Hongyan Huang4, Xiaoning Wang1,5, Qiang Sun2,6
1School of Biology and Biological Engineering, South China University of Technology,
2Laboratory of Cell Engineering, Institute of Biotechnology,
3307 Hospital, 307 Hospital,
4Department of Oncology, Beijing Shijitan Hospital of Capital Medical University,
5The Key Laboratory of Normal aging & Geriatric, the Chinese PLA General Hospital,
6Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an 710032, P. R. China.
Abstract
Homotypic cell-in-cell (CIC) structures formed 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. Here, we performed microarray analysis to identify genes associated with homotypic CIC formation. Cancer cells differing in their abilities 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 attenuated by IL-8 knockdown and enhanced upon recombinant IL-8 treatment, which was correlated with altered cell-cell adhesion and expression of adhesive molecules such as P-cadherin and ャ-catenin. Together, our work identified IL-8 as a positive regulator of homotypic CIC formation via enhancing intercellular adhesion.
Abstract, Accepted Manuscript(in press) [Submitted on April 22, 2018, Accepted on July 2, 2018]
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