Discoidin domain receptor tyrosine kinases: new players in cancer progression.
Discoidin domain receptor tyrosine kinases: new players in cancer progression.
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DOI：
10.1007/s10555-012-9346-z
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发表时间：
2012-06
影响因子：
9.2
通讯作者：
Fridman, Rafael
中科院分区：
文献类型：
--
作者：
Valiathan, Rajeshwari R.;Marco, Marta;Leitinger, Birgit;Kleer, Celina G.;Fridman, Rafael
关键词：
几乎所有的人类癌症都显示一种或多种受体酪氨酸激酶（RTK）的表达和/或功能失调。RTK功能改变与癌症进展之间的强因果关系已转化为靶向这些细胞表面受体治疗癌症的新治疗策略。然而，可能改变致癌过程的RTKs的全谱尚未完全了解。越来越多的证据表明，一组独特的RTK被称为盘状结构域受体（DDRs）通过调节肿瘤细胞与其周围胶原基质的相互作用在癌症进展中发挥作用。DDR是唯一特异性结合胶原并被胶原激活的RTK。因此，DDR是信号传导网络的一部分，其翻译来自细胞外基质的信息，从而充当细胞-基质相互作用的关键调节剂。在生理条件下，DDR通过充当胶原蛋白传感器、转导调节细胞极性、组织形态发生和细胞分化的信号来控制细胞和组织稳态。在癌症中，DDR被肿瘤细胞劫持以破坏正常的细胞基质通信并启动促迁移和促侵入程序。重要的是，几种癌症类型表现出DDR突变，这被认为会改变受体功能并促进癌症进展。其他证据表明，DDR在癌症中的作用是复杂的，以DDR类型/同种型特异性和环境依赖性方式促进或抑制肿瘤细胞行为。因此，我们对DDR在癌组织中的作用的认识仍有相当大的差距。本文综述了DDR在癌症中的表达和功能，并讨论了DDR在癌症生物学中的潜在意义。希望这一努力将鼓励对这些知之甚少但独特的RTK进行更多的研究，这些RTK有可能成为癌症的新治疗靶点。
Almost all human cancers display dysregulated expression and/or function of one or more receptor tyrosine kinases (RTKs). The strong causative association between altered RTK function and cancer progression has translated into novel therapeutic strategies that target these cell surface receptors in the treatment of cancer. Yet, the full spectrum of RTKs that may alter the oncogenic process is not completely understood. Accumulating evidence suggests that a unique set of RTKs known as the Discoidin Domain Receptors (DDRs) play a role in cancer progression by regulating the interactions of tumor cells with their surrounding collagen matrix. The DDRs are the only RTKs that specifically bind to, and are activated by collagen. Hence, the DDRs are part of the signaling networks that translate information from the extracellular matrix thereby acting as key regulators of cell-matrix interactions. Under physiological conditions, DDRs control cell and tissue homeostasis by acting as collagen sensors, transducing signals that regulate cell polarity, tissue morphogenesis, and cell differentiation. In cancer, DDRs are hijacked by tumor cells to disrupt normal cell-matrix communication and initiate pro-migratory and pro-invasive programs. Importantly, several cancer types exhibit DDR mutations, which are thought to alter receptor function and contribute to cancer progression. Other evidence suggests that the actions of DDRs in cancer are complex, either promoting or suppressing tumor cell behavior in a DDR type/isoform specific and context dependent manner. Thus, there is still a considerable gap in our knowledge of DDR actions in cancer tissues. This review summarizes the current knowledge on DDR expression and function in cancer and discusses the potential implications of DDRs in cancer biology. It is hoped that this effort will encourage more research into these poorly understood but unique RTKs, which have the potential of becoming novel therapeutics targets in cancer.
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影响因子：
24.5
作者：
Badiola, Iker;Olaso, Elvira;Vidal-Vanaclocha, Fernando
通讯作者：
Vidal-Vanaclocha, Fernando
DOI：
10.1016/j.str.2009.10.012
发表时间：
2009-12-09
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Carafoli F;Bihan D;Stathopoulos S;Konitsiotis AD;Kvansakul M;Farndale RW;Leitinger B;Hohenester E
通讯作者：
Hohenester E
影响因子：
14
作者：
Bhadriraju, Kiran;Chung, Koo-Hyun;Plant, Anne L.
通讯作者：
Plant, Anne L.
影响因子：
9.8
作者：
Bargal, Ruth;Cormier-Daire, Valerie;Raas-Rothschild, Annick
通讯作者：
Raas-Rothschild, Annick
影响因子：
5.6
作者：
Agarwal, Gunjan;Mihai, Cosmin;Iscru, Daniel F.
通讯作者：
Iscru, Daniel F.