Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8304962 | Biochimie | 2015 | 9 Pages |
Abstract
Oligosaccharides on the surface of adhesion molecules may contribute to the process of CAM-DR. To investigate the role of the Lewis y antigen in this process, we established a cell adhesion model mediated by the integrin α5β1-FN interaction in the ovarian cancer cell line, RMG-1-hFUT, which highly expresses Lewis y by transfection with α1,2-fucosyltransferase into RMG-1 cells. Our results indicate that the rates of carboplatin-induced apoptosis and necrosis are reduced in FN-adhered tumor cells, and carboplatin resistance is significantly decreased in the presence of anti-Lewis y antibody. CAM-DR in tumor cells has been correlated with elevated expression of the nuclear anti-apoptotic proteins Bcl-2 and Bcl-XL. Lewis y promotes the expression of the Bcl-2 and Bcl-XL genes by activating the focal adhesion kinase signaling pathway and accelerating their transcription. Thus, Lewis y leads to inhibition of apoptosis and enhancement of CAM-DR by activation of the FAK signaling pathway and upregulation of Bcl-2/Bcl-XL expression in ovarian cancer cell lines.
Keywords
ECMPI3KCAM-DRcell adhesion-mediated drug resistanceFAKRT-PCRBcl-2ERKTGFMAPKAkttransforming growth factorPhosphatidyl Inositol 3-kinaseFibronectinLewis YExtracellular matrixreverse transcription-polymerase chain reactionprotein kinase Bmitogen-activated protein kinaseextracellular signal-regulated kinasesfocal adhesion kinase
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Authors
Limei Yan, Changzhi Wang, Bei Lin, Juanjuan Liu, Dawo Liu, Rui Hou, Yifei Wang, Lili Gao, Shulan Zhang, Masao Iwamori,