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

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

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: linbei88@hotmail.com.
  • 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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