Lewis y enhances CAM-DR in ovarian cancer cells by activating the FAK signaling pathway and upregulating Bcl-2/Bcl-XL expression.
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.
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
Limei
L
Yan
Department of Obstetrics and Gynecology, Shantou University Medical College, Shantou 515000, PR China.
Changzhi
C
Wang
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China. Electronic address: linbei88@hotmail.com.
Bei
B
Lin
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
Juanjuan
J
Liu
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
Dawo
D
Liu
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
Rui
R
Hou
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, PR China.
Yifei
Y
Wang
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
Lili
L
Gao
Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, PR China.
Shulan
S
Zhang
Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Masao
M
Iwamori
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics
C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
Bcl-2; CAM-DR; FAK signaling pathway; Integrin α5β1; Lewis y