Lewis Y regulates signaling molecules of the transforming growth factor β pathway in ovarian carcinoma-derived RMG-I cells

• Published in: International journal of oncology Vol. 40; no. 4; pp. 1196 - 1202
• Main Authors: LI, FEI-FEI, LIU, JUAN-JUAN, LIU, DA-WO, LIN, BEI, HAO, YING-YING, CONG, JIAN-PING, ZHU, LIAN-CHENG, GAO, SONG, ZHANG, SHU-LAN, IWAMORI, MASAO
• Format: Journal Article
• Language: English
• Published: Athens D.A. Spandidos 01.04.2012; Editorial Academy of the International Journal of Oncology
• Subjects: Animals; Biological and medical sciences; Cell Growth Processes - physiology; Cell Line, Tumor; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Lewis Blood-Group System - genetics; Lewis Blood-Group System - metabolism; Lewis Y; Medical sciences; Mice; Mice, Inbred BALB C; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; p42/44 mitogen-activated protein kinase; phosphoinositide 3-kinase; Signal Transduction; Smad; Transfection; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; transforming growth factor β type I (II) receptor; Tumors; Ovary carcinoma; Smad protein; transforming growth factor β type I (II) receptor; Enzyme; Transforming growth factor β; Transferases; Ovary cancer; Mitogen-activated protein kinase; Malignant tumor; Female genital diseases; 1-Phosphatidylinositol 3-kinase; Lewis Y; Ovarian diseases; Signal transduction; Blood group; Cancerology; Smad; p42/44 mitogen-activated protein kinase; phosphoinositide 3-kinase; Cancer; Biological receptor
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2011.1296

LeY (Lewis Y) is a difucosylated oligosaccharide carried by glycoconjugates on the cell surface. Elevation of LeY is frequently observed in epithelial-derived cancers and is correlated to pathological staging and prognosis. To study the role of LeY on cancer cells, a stably LeY-overexpressing cell line, RMG-I-H, was developed previously by transfection of the α1,2-fucosyltransferase gene, a key enzyme that catalyzes the synthesis of LeY, into ovarian carcinoma-derived RMG-I cells. Our studies have shown that LeY is involved in the changes in biological behavior of RMG-I-H cells. However, the mechanism is still largely unknown. In this study, we determined the structural relationship and co-localization between LeY and TβRI/TβRII, respectively, and the potential cellular signaling mechanism was also investigated. We found that both TβRI and TβRII contain the LeY structure, and the level of LeY in TβRI and TβRII in RMG-I-H cells was significantly increased. Overexpression of LeY up-regulates the phosphorylation of ERK, Akt and down-regulates the phosphorylation of Smad2/3. In addition, the phosphorylation intensity was attenuated significantly by LeY monoantibody. These findings suggest that LeY is involved in the changes in biological behavior through TGF-β receptors via Smad, ERK/MAPK and PI3K/Akt signaling pathways. We suggest that LeY may be an important composition of growth factor receptors and could be an attractive candidate for cancer diagnosis and treatment.