Expression profiling identified IL-8 as a regulator of homotypic cell-in-cell formation
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
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.
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 γ-catenin. Together, our work identified IL-8 as a positive regulator of homotypic CIC formation via enhancing intercellular adhesion.
참고문헌 (15)
- Wang S, "Internalization of NK cells into tumor cells requires ezrin and leads to programmed cell-in-cell death", Cell Res, 19, pp.1350~1362 (2009)[DOI]
- Huang H, "Mammalian cell competitions, cell-in-cell phenomena and their biomedical implications", Curr Mol Med, 15, pp.852~860 (2015)[DOI]
- Sun Q, "Cell-in-cell structures are involved in the competition between cells in human tumors", Mol Cell Oncol, 2, pp.e1002707~ (2015)[DOI]
- Sun Q, "Competition between human cells by entosis", Cell Res, 24, pp.1299~1310 (2014)[DOI]
- Overholtzer M, "A nonapoptotic cell death process, entosis, that occurs by cell-in-cell invasion", Cell, 131, pp.966~979 (2007)[DOI]
- Ning X, "The physics for the formation of cell-in-cell structures", Curr Mol Med, 15, pp.867~872 (2015)[DOI]
- Wang M, "Impaired formation of homotypic cell-in-cell structures in human tumor cells lacking alpha-catenin expression", Sci Rep, 5, pp.12223~ (2015)[DOI]
- Sun Q, "Induction of entosis by epithelial cadherin expression", Cell Res, 24, pp.1288~1298 (2014)[DOI]
- Ruan B, "Cholesterol inhibits entotic cell-in-cell formation and actomyosin contraction", Biochem Biophys Res Commun, 495, pp.1440~1446 (2018)[DOI]
- Hamann JC, "Entosis Is Induced by Glucose Starvation", Cell Rep, 20, pp.201~210 (2017)[DOI]
- Cano CE, "Homotypic cell cannibalism, a cell-death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer", EMBO Mol Med, 4, pp.964~979 (2012)[DOI]
- Galluzzi L, "Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018", Cell Death Differ, 25, pp.486~541 (2018)[DOI]
- Martins I, "Entosis: The emerging face of non-cell-autonomous type IV programmed death", Biomed J, 40, pp.133~140 (2017)[DOI]
- David JM, "The IL-8", IL-8R axis: a double agent in tumor immune resistance, 2016, pp.4, ~
- Fernando RI, "IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells", Cancer Res, 71, pp.5296~5306 (2011)[DOI]