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作 者:常琳琳[1] 朱虹[1] 郑琳[1] 曹戟[1] 罗沛华[1] 何俏军[1]
机构地区:[1]浙江大学药学院浙江省抗肿瘤药物临床前研究重点实验室,浙江杭州310058
出 处:《药学进展》2015年第10期754-760,共7页Progress in Pharmaceutical Sciences
基 金:浙江省卫生厅高层次创新人才基金
摘 要:E-cadherin参与形成细胞间黏附性连接,是胚胎发育过程中的一个关键因子。越来越多的研究表明,E-cadherin在肿瘤的发生发展过程中也发挥了至关重要的作用。在生物体内,E-cadherin的表达和功能受到多个水平、多重因素的调控,而E-cadherin又可以影响多条重要信号通路的活性,参与到多种生理病理过程中。E-cadherin下调造成细胞间黏附性连接减少、极性减弱,细胞由上皮样转变为间质样,这一变化是上皮间质转化(EMT)的重要标志之一。E-cadherin与多种肿瘤的发生有一定的相关性。同时E-cadherin下调所引起的EMT促进肿瘤细胞的迁移运动,肿瘤细胞侵袭力增强,促进转移的发生。近年来,大量研究关注到E-cadherin对肿瘤细胞的耐药及干细胞特性的获得都有影响。综述E-cadherin在肿瘤发生发展中的作用,探讨以E-cadherin为靶点的肿瘤治疗的现状及展望。E-cadherin, an intercellular adhesion molecule, plays critical roles during embryonic development. Mounting evidences have revealed that E-cadherin is also involved extensively in the development and progression of cancer. E-eadherin expression and fi.mction are tightly controlled by multiple factors at multiple levels. Furthermore, E-cadherin is capable of regulating multiple important signaling pathways and involved in a variety of physiological and pathological processes. The downregulation of E-cadherin results in less intercellular adhesion and reduced cell polarity. Consequently, epithelial cells become mesenchymal stem cells, which is one of the hallmarks of epithelial-mesenehymal transition (EMT). Thus it has been proposed the correlation between the expression of E-eadherin and the malignance of tumors. E-cadherin downregulation-induced EMT facilitates the migration, invasion and metastasis of tumor cells. In addition, recent evidences have suggested that E-cadherin reduction also leads to drug resistance and increased stem cell properties of tumor cells. Based on these studies, the current review summarizes the roles of E-cadherin in carcinogenesis and cancer progression, and explores the current situation and future prospects of cancer therapy targeting E-eadherin.
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