Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation.
Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation.
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表达谱鉴定 IL-8 是同型细胞内形成的调节因子
DOI：
10.5483/bmbrep.2018.51.8.089
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发表时间：
2018-08
期刊：
影响因子：
3.8
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Ruan B;Wang C;Chen A;Liang J;Niu Z;Zheng Y;Fan J;Gao L;Huang H;Wang X;Sun Q
在癌细胞之间形成的同型细胞中细胞(CIC)结构被认为是通过内陷(一种非凋亡性细胞死亡过程)来促进肿瘤的进化。然而，它们形成的机制仍然知之甚少。我们进行了微阵列分析，以确定与同型CIC形成相关的基因。选择形成同型CIC结构能力不同的癌细胞进行研究。关联分析确定了62个候选基因的73个探针组，这些基因可能参与CIC的形成。其中，21个基因表达下调，41个基因表达上调。通路分析确定了一个以IL-8为中心的基因相互作用网络，该网络在高CIC细胞中上调。IL-8可显著抑制CIC的形成，重组IL-8可促进CIC的形成，这与P-钙粘蛋白和γ-连环蛋白等黏附分子的表达改变有关。总之，我们的工作确认IL-8是通过增强细胞间黏附而形成同型CIC的积极调节因子。
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 γ-catenin. Together, our work identified IL-8 as a positive regulator of homotypic CIC formation via enhancing intercellular adhesion.