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liruihan鐵桿木蟲 (正式寫手)
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【資源】GlcNAcylation在乳腺癌轉(zhuǎn)移中發(fā)揮重要作用 已有1人參與
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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
鐵桿木蟲 (正式寫手)
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GlcNAcylation在乳腺癌轉(zhuǎn)移中發(fā)揮重要作用 GlcNAcylation 是一種動態(tài)的翻譯后修飾廣泛參與了生物過程和某些疾病的發(fā)生。盡管越來越多的證據(jù)顯示某些腫瘤相關(guān)蛋白可被GlcNAcylation 修飾，但GlcNAcylation 在腫瘤進展中的作用還不清楚。本研究中我們發(fā)現(xiàn)GlcNAcylation 可增強體外乳腺癌細胞的遷移/侵襲和體內(nèi)肺轉(zhuǎn)移灶的形成。E-cadherin細胞表面表達的降低時GlcNAcylation 誘導(dǎo)的乳腺癌轉(zhuǎn)移的分子機制。P120和β-catenin，而不是E-cadherin是GlcNAcylated,p120和β-catenin可能在降低細胞表面E-cadherin的表達中發(fā)揮作用。而且，免疫組化分析顯示乳腺腫瘤組織中全GlcNAcylation水平明顯高于對應(yīng)的鄰近組織，在轉(zhuǎn)移性淋巴結(jié)腫餓表達明顯高于對應(yīng)的原發(fā)腫瘤。這是首次報道并闡明了GlcNAcylation增強乳腺癌細胞侵襲轉(zhuǎn)移的作用及機制。這些結(jié)果也支持GlcNAcylation可能在乳腺癌診斷和治療中是一個潛在的靶點。 |
2樓2010-07-11 09:32:41
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