Lewis y enhances CAM-DR in ovarian cancer cells by activating the FAK signaling pathway and upregulating Bcl-2/Bcl-XL expression

  • Biochimie. 2015 Jun;113:17-25. doi: 10.1016/j.biochi.2015.01.013.
Limei Yan  1 ,  Changzhi Wang  2 ,  Bei Lin  3 ,  Juanjuan Liu  1 ,  Dawo Liu  1 ,  Rui Hou  1 ,  Yifei Wang  4 ,  Lili Gao  1 ,  Shulan Zhang  1 ,  Masao Iwamori  5
Affiliations
  • 1. Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
  • 2. Department of Obstetrics and Gynecology, Shantou University Medical College, Shantou 515000, PR China.
  • 3. Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China. Electronic address: [email protected].
  • 4. Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, PR China.
  • 5. Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.
PMID: 25726913 DOI: 10.1016/j.biochi.2015.01.013
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
Bcl-2; CAM-DR; FAK signaling pathway; Integrin α5β1; Lewis y.
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