Par Proteins in Tumor Formation and Progression
Par Proteins in Tumor Formation and Progression
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DOI：
10.1007/978-3-319-14466-5_6
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
M. Mescher;S. Iden
中科院分区：
文献类型：
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作者：
M. Mescher;S. Iden
进化保守的分割缺陷(PAR)基因家族的蛋白质已经成为极性的关键调节因子，从而成为细胞和组织结构的关键调节因子。PAR蛋白介导多种细胞过程，并将细胞形状的控制与调节生长和存活、新陈代谢、细胞命运和分化的关键信号通路结合起来。肿瘤细胞的粘附性、极性和构型的改变是癌症的特征，并与肿瘤的生长、侵袭和转移有关。在果蝇和哺乳动物细胞培养中的开创性工作表明，极性的调节和致癌过程之间存在分子联系。最近的进展来自不同的小鼠模型，揭示了极性蛋白质功能障碍与癌症形成和进展之间的因果联系，开始揭示一些潜在的机制。很明显，极性信号影响肿瘤形成和进展的多种过程，并且存在显著的上下文依赖性。本章提供了当受到干扰时促进肿瘤形成的生理过程的概述。本文总结了最近来自模式生物的证据，这些证据表明PAR蛋白功能障碍与癌症的发生和发展有关。由于PAR蛋白与aPKC信号通路紧密相连，因此也提供了有关aPKC在癌症中的作用的数据。本章将回顾来自无脊椎动物肿瘤模型的重要发现，尽管这一章侧重于来自哺乳动物系统的功能数据。
Proteins of the evolutionary conserved family of partitioning-defective (Par) genes have emerged as key regulators of polarity and thus of cell and tissue architecture. Par proteins mediate a variety of cellular processes and couple control of cell shape to crucial signaling pathways regulating growth and survival, metabolism, cell fate, and differentiation. Alterations in adhesion, polarity, and architecture of tumor cells are hallmarks of cancer and implicated in tumor growth, invasion, and metastasis. Seminal work inDrosophilaand mammalian cell culture suggested a molecular connection between the regulation of polarity and oncogenic processes. Recent advance stems from different mouse models revealing a causal link between polarity protein dysfunction and the formation and progression of cancer starting to shed light into some underlying mechanisms. It has become apparent that polarity signaling impacts on a multitude of processes involved in tumor formation and progression and that significant context dependency exists.This chapter provides an overview of physiological processes that when disturbed facilitate tumor formation. Recent evidence from model organisms implicating Par protein dysfunction in the onset and progression of cancer is summarized. As Par proteins are tightly connected to aPKC signalling, data regarding a role of aPKC in cancer is also presented. Important findings from invertebrate tumor models will be reviewed, though the chapter focuses on functional data derived from mammalian systems.