Linking Autophagy and the Dysregulated NFκB/ SNAIL/YY1/RKIP/PTEN Loop in Cancer: Therapeutic Implications.
Linking Autophagy and the Dysregulated NFκB/ SNAIL/YY1/RKIP/PTEN Loop in Cancer: Therapeutic Implications.
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DOI：
10.1615/critrevoncog.2018027212
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发表时间：
2018
影响因子：
--
通讯作者：
Bonavida B
中科院分区：
文献类型：
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作者：
Bonavida B
自噬在各种癌症的发病机制中的作用已经在许多报告中得到了很好的证明。癌细胞中的自噬调节细胞增殖、活力、侵袭、上皮向间质转化（EMT）、转移以及对化学治疗和免疫治疗策略的响应。这些表现是各种调控自噬、生物化学和分子机制的基因产物的结果。在几种人类癌细胞模型中，存在失调的回路-即NFκB/SNAIL/YY 1/RKIP/PTEN-其在调节肿瘤细胞的独特特征中起主要作用，所述独特特征刚刚被列出用于自噬调节活性。因此，癌细胞中的自噬机制和失调回路具有许多相同的性质和活性。因此，有人假设两者之间一定存在生物化学/分子联系。本综述介绍了链接和关联的失调电路的每个基因产物与自噬机制，并划定串扰的存在。自噬和失调电路之间的串扰是显著的，并且在针对癌细胞中的自噬或失调基因产物的靶向疗法的开发中具有重要意义。
The role of autophagy in the pathogenesis of various cancers has been well documented in many reports. Autophagy in cancer cells regulates cell proliferation, viability, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, and responses to chemotherapeutic and immunotherapeutic treatment strategies. These manifestations are the result of various regulatory gene products that govern autophagic, biochemical, and molecular mechanisms. In several human cancer cell models, the presence of a dysregulated circuit—namely, NFκB/SNAIL/YY1/RKIP/PTEN—that plays a major role in the regulation of tumor cell unique characteristics just listed for autophagy-regulated activities. Accordingly, the autophagic mechanism and the dysregulated circuit in cancer cells share many of the same properties and activities. Thus, it has been hypothesized that there must exist a biochemical/molecular link between the two. The present review describes the link and the association of each gene product of the dysregulated circuit with the autophagic mechanism and delineates the presence of crosstalk. Crosstalk between autophagy and the dysregulated circuit is significant and has important implications in the development of targeted therapies aimed at either autophagy or the dysregulated gene products in cancer cells.