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【资源】GlcNAcylation在乳腺癌转移中发挥重要作用 已有1人参与
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GlcNAcylation Plays an Essential Role in Breast Cancer Metastasis GlcNAcylation, a dynamic posttranslational modification, is involved in a wide range of biological processes and some human diseases. Although there is emerging evidence that some tumor-associated proteins are modified by GlcNAcylation, the role of GlcNAcylation in tumor progression remains unclear. Here, we show that GlcNAcylation enhances the migration/invasion of breast cancer cells in vitro and lung metastasis in vivo. The decrease of cell surface E-cadherin is the molecular mechanism underlying GlcNAcylation-induced breast cancer metastasis. p120 and β-catenin, but not E-cadherin, are GlcNAcylated; the GlcNAcylation of p120 and β-catenin might play roles in the decrease of cell surface E-cadherin. Moreover, immunohistochemistry analysis indicated that the global GlcNAcylation level in breast tumor tissues is elevated significantly as compared with that in the corresponding adjacent tissues; further, GlcNAcylation was significantly enhanced in metastatic lymph nodes compared with their corresponding primary tumor tissues. This is the first report to clearly elucidate the roles and mechanisms whereby GlcNAcylation influences the malignant properties of breast cancer cells. These results also suggest that GlcNAcylation might be a potential target for the diagnosis and therapy of breast cancer. Cancer Res; 70(15); OF1–8. ©2010 AACR. |
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liruihan
铁杆木虫 (正式写手)
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GlcNAcylation在乳腺癌转移中发挥重要作用 GlcNAcylation 是一种动态的翻译后修饰广泛参与了生物过程和某些疾病的发生。尽管越来越多的证据显示某些肿瘤相关蛋白可被GlcNAcylation 修饰，但GlcNAcylation 在肿瘤进展中的作用还不清楚。本研究中我们发现GlcNAcylation 可增强体外乳腺癌细胞的迁移/侵袭和体内肺转移灶的形成。E-cadherin细胞表面表达的降低时GlcNAcylation 诱导的乳腺癌转移的分子机制。P120和β-catenin，而不是E-cadherin是GlcNAcylated,p120和β-catenin可能在降低细胞表面E-cadherin的表达中发挥作用。而且，免疫组化分析显示乳腺肿瘤组织中全GlcNAcylation水平明显高于对应的邻近组织，在转移性淋巴结肿饿表达明显高于对应的原发肿瘤。这是首次报道并阐明了GlcNAcylation增强乳腺癌细胞侵袭转移的作用及机制。这些结果也支持GlcNAcylation可能在乳腺癌诊断和治疗中是一个潜在的靶点。 |
2楼2010-07-11 09:32:41