期刊
MOLECULAR CANCER RESEARCH
卷 8, 期 11, 页码 1526-1535出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-10-0302
关键词
-
资金
- Association pour la Recherche sur le Cancer [7936, 5023, 1137]
- la Ligue regionale contre le Cancer
- PAI Hubert Curien France-Korea STAR
- l'ANR-Young Investigator Program
The disialoganglioside G(D3) is overexpressed in similar to 50% of invasive ductal breast carcinoma, and the G(D3) synthase gene (ST8SIA1) displays higher expression among estrogen receptor-negative breast cancer tumors, associated with a decreased overall survival of breast cancer patients. However, no relationship between ganglioside expression and breast cancer development and aggressiveness has been reported. We have previously shown that overexpression of G(D3) synthase induces the accumulation of b- and c-series gangliosides (G(D3), G(D2), and G(T3)) at the cell surface of MDA-MB-231 breast cancer cells together with the acquisition of a proliferative phenotype in the absence of serum. Here, we show that phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways are constitutively activated in G(D3) synthase-expressing cells. Analysis of phosphorylation of tyrosine kinase receptors shows a specific c-Met constitutive activation in G(D3) synthase-expressing cells, in the absence of its ligand, hepatocyte growth factor/scatter factor. In addition, inhibition of c-Met or downstream signaling pathways reverses the proliferative phenotype. We also show that G(D3) synthase expression enhances tumor growth in severe combined immunodeficient mice. Finally, a higher expression of ST8SIA1 and MET in the basal subtype of human breast tumors are observed. Altogether, our results show that G(D3) synthase expression is sufficient to enhance the tumorigenicity of MDA-MB-231 breast cancer cells through a ganglioside-dependent activation of the c-Met receptor. Mol Cancer Res; 8(11); 1526-35. (C) 2010 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据