Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance.
Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance.
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DOI：
10.1016/j.gendis.2015.12.004
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发表时间：
2016-03
期刊：
影响因子：
6.8
通讯作者：
Lee MJ
中科院分区：
文献类型：
--
作者：
Mohammed MK;Shao C;Wang J;Wei Q;Wang X;Collier Z;Tang S;Liu H;Zhang F;Huang J;Guo D;Lu M;Liu F;Liu J;Ma C;Shi LL;Athiviraham A;He TC;Lee MJ
Wnt信号传导转导了在进化上保守的通路，这些通路在启动和调节多种细胞活动中发挥重要作用，包括细胞增殖、钙稳态和细胞极性。Wnt信号在控制细胞增殖和干细胞自我更新方面的作用主要通过经典通路实现，经典通路是多个Wnt信号分支中特征最为明确的。在过去的10年里，我们对该通路复杂性的理解迅速扩展，因为许多Wnt信号的新成分已被确定，并与信号调节、干细胞功能以及成体组织稳态相关联。此外，大量证据将Wnt信号与多种癌症类型的肿瘤发生联系起来，并表明其与癌症耐药性的发展有关。因此，更好地理解Wnt信号失调在人类癌症发生和进展之前的机制可能会加速通路抑制剂的开发，以增强当前的治疗。本综述总结和综合了我们目前对经典Wnt通路在发育和疾病中的认识。我们首先概述经典Wnt信号通路的组成成分，然后深入探讨该通路在干性、肿瘤发生和癌症耐药性中所起的作用。最终，我们希望呈现一组有条理的证据，表明Wnt信号与肿瘤发生和化疗耐药性有关，以促进对Wnt通路调节剂的研究，这些调节剂可能改善Wnt信号导致侵袭性疾病和/或治疗耐药的癌症的治疗结果。
Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities, including cell proliferation, calcium homeostasis, and cell polarity. The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway, which is the best-characterized the multiple Wnt signaling branches. The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway, as many new components of Wnt signaling have been identified and linked to signaling regulation, stem cell functions, and adult tissue homeostasis. Additionally, a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance. Thus, a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy. This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease. We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness, tumorigenesis, and cancer drug resistance. Ultimately, we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.