Emerging roles of claudins in human cancer.
Emerging roles of claudins in human cancer.
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DOI：
10.3390/ijms140918148
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发表时间：
2013-09-04
影响因子：
5.6
通讯作者：
Kwon MJ
中科院分区：
文献类型：
--
作者：
Kwon MJ
claudin是紧密连接的主要整体膜蛋白。一些claudin蛋白表达的改变，特别是claudin-1、-3、-4和-7，与各种癌症的发生有关。虽然它们在癌症中的失调表明claudin在肿瘤发生中起作用，但确切的潜在机制尚不清楚。claudin以组织依赖的方式参与癌细胞的迁移、侵袭和转移，表明其参与肿瘤进展。最近的研究表明，它们在上皮到间充质转化（EMT）、癌症干细胞或肿瘤起始细胞（CSCs/TICs）的形成和化疗耐药中发挥作用，表明cladin是治疗化疗耐药和复发性肿瘤的有希望的靶点。最近发现的一种以EMT和干细胞样特征富集为特征的低claudin乳腺癌亚型与疾病复发显著相关，强调了claudin作为肿瘤复发预测因子的重要性。表观遗传机制在claudin表达调控中的关键作用表明表观遗传治疗可能应用于靶claudin。更好地了解cladin在CSC/ tic和化疗耐药中的新作用可能有助于开发针对复发性癌症的治疗方法。
Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. The critical role of epigenetic mechanisms in the regulation of claudin expression indicates the possible application of epigenetic therapy to target claudins. A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against recurrent cancers.
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