Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, PR China.
Int J Oncol. 2012 Apr;40(4):1196-202. doi: 10.3892/ijo.2011.1296. Epub 2011 Dec 13.
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.
LeY(Lewis Y)是一种在细胞表面糖缀合物上携带的双岩藻糖基化寡糖。LeY 的升高在上皮来源的癌症中经常观察到,与病理分期和预后相关。为了研究 LeY 对癌细胞的作用,先前通过将α1,2-岩藻糖基转移酶基因(催化 LeY 合成的关键酶)转染到卵巢癌细胞衍生的 RMG-I 细胞中,开发了一种稳定过表达 LeY 的细胞系 RMG-I-H。我们的研究表明,LeY 参与了 RMG-I-H 细胞生物学行为的变化。然而,其机制在很大程度上仍然未知。在这项研究中,我们分别确定了 LeY 与 TβRI/TβRII 之间的结构关系和共定位,还研究了潜在的细胞信号机制。我们发现,TβRI 和 TβRII 均含有 LeY 结构,并且 RMG-I-H 细胞中 TβRI 和 TβRII 中的 LeY 水平显着增加。LeY 的过表达上调了 ERK、Akt 的磷酸化,下调了 Smad2/3 的磷酸化。此外,LeY 单克隆抗体显着减弱了磷酸化强度。这些发现表明,LeY 通过 TGF-β 受体通过 Smad、ERK/MAPK 和 PI3K/Akt 信号通路参与了生物学行为的变化。我们建议,LeY 可能是生长因子受体的重要组成部分,可能是癌症诊断和治疗的有吸引力的候选物。