Wnt/catenin signaling in adult stem cell physiology and disease.
Wnt/catenin signaling in adult stem cell physiology and disease.
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DOI：
10.1007/s12015-014-9515-2
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发表时间：
2014-08
影响因子：
4.8
通讯作者：
Kahn, Michael
中科院分区：
文献类型：
--
作者：
Ring, Alexander;Kim, Yong-Mi;Kahn, Michael
关键词：
Wnt信号在发育和疾病中起着重要作用。在这篇综述中，我们重点介绍了经典的Wnt信号通路在体干细胞生物学中的作用及其在组织稳态中的关键作用。我们目前的知识Wnt/β-catenin信号如何影响组织干细胞的行为在各种器官系统，包括肠道，乳腺，造血和神经系统。我们讨论的证据表明，经典的Wnt信号既可以保持效力和未分化状态，以及在体干细胞的分化，这取决于细胞和环境的背景。基于本实验室和其他实验室的研究，我们将试图解释该信号通路在决定细胞命运决定中的二分行为，并特别强调β-catenin与两种高度同源的辅激活蛋白CBP和p300的相互作用，以阐明它们在Wnt/β-catenin信号通路结果中的差异作用。此外，我们回顾了目前的知识，关于Wnt/β-catenin信号在癌症生物学中的异常调节，特别是其在癌症干细胞中的关键作用。最后，我们讨论的数据表明，β-连环蛋白/共激活因子相互作用的小分子调节剂可用于改变未分化的增殖和分化之间的平衡，这可能是一个有前途的治疗方法，以干细胞为基础的疾病机制。
Wnt signaling plays an important role in development and disease. In this review we focus on the role of the canonical Wnt signaling pathway in somatic stem cell biology and its critical role in tissue homeostasis. We present current knowledge how Wnt/β-catenin signaling affects tissue stem cell behavior in various organ systems, including the gut, mammary gland, the hematopoietic and nervous system. We discuss evidence that canonical Wnt signaling can both maintain potency and an undifferentiated state as well as cause differentiation in somatic stem cells, depending on the cellular and environmental context. Based on studies by our lab and others, we will attempt to explain the dichotomous behavior of this signaling pathway in determining cell fate decisions and put special emphasis on the interaction of β-catenin with two highly homologous co-activator proteins, CBP and p300, to shed light on the their differential role in the outcome of Wnt/β-catenin signaling. Furthermore, we review current knowledge regarding the aberrant regulation of Wnt/β-catenin signaling in cancer biology, particularly its pivotal role in the context of cancer stem cells. Finally, we discuss data demonstrating that small molecule modulators of the β-catenin/co-activator interaction can be used to shift the balance between undifferentiated proliferation and differentiation, which potentially presents a promising therapeutic approach to stem cell based disease mechanisms.
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DOI：
10.1023/b:jomg.0000037157.94207.33
发表时间：
2004-04-01
影响因子：
2.5
作者：
Brennan, KR;Brown, AMC
通讯作者：
Brown, AMC
影响因子：
5.2
作者：
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通讯作者：
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影响因子：
46.9
作者：
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Benvenisty, Nissim
影响因子：
8.9
作者：
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通讯作者：
Leri, Annarosa
影响因子：
16.2
作者：
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通讯作者：
Wilson SW