ER-Golgi network--a future target for anti-cancer therapy.
ER-Golgi network--a future target for anti-cancer therapy.
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DOI：
10.1016/j.leukres.2009.05.025
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发表时间：
2009-11
影响因子：
2.7
通讯作者：
Darzynkiewicz Z
中科院分区：
文献类型：
--
作者：
Wlodkowic D;Skommer J;McGuinness D;Hillier C;Darzynkiewicz Z
肿瘤细胞死亡是消除异常恶性细胞的重要事件，并提供了天然肿瘤抑制的重要机制。使这些精细调节的过程丧失能力为癌症克隆成功地逃避生理控制系统和治疗干预提供了强大的优势。扩大我们对调节肿瘤细胞死亡的分子“交叉对话”的了解对于指导未来抗癌疗法的成功设计至关重要。尽管目前可用的数据表明，恶性细胞的消除通常取决于经典的凋亡途径（线粒体和/或死亡受体途径），但越来越多的证据表明，替代性凋亡和非凋亡途径可能有效地促进肿瘤细胞死亡。假设每个细胞器都能够感知，放大和执行细胞死亡也是一个相对新颖和未探索的概念。如最近所示，分泌途径可以积极参与感知应激刺激，甚至可能启动和传播细胞死亡信号。实验证据表明，ER和高尔基体可以激活两个促生存（恢复）机制，以及细胞自杀程序，如果压力信号阈值被超过。因此，可以想象，各种亚细胞区室之间蛋白质运输的脆弱平衡提供了一个特殊的治疗机会。有趣的是，越来越多的报道认识到新的治疗靶点，包括控制内质网（ER）和高尔基体稳态的蛋白质。然而，需要进一步的研究来阐明从ER-高尔基体隔室发出的精确信号通路。还需要开发更有效和选择性的小分子药物来激活ER-高尔基体介导的细胞死亡。由于在癌细胞死亡过程中ER-高尔基体网络的作用的兴趣已经获得了动力，我们试图在这里批判性地评价目前的研究抗癌药物的发展状况，靶向ER和/或高尔基体。
Tumor cell demise is an important event in the elimination of abnormal malignant cells and provides an important mechanism of natural tumor suppression. Abnormalities incapacitating these finely tuned processes provide a strong advantage for cancer clones to succeed in evading both the physiological control systems and therapeutic intervention. Expanding our knowledge of the molecular “cross-talks” that regulate tumor cell demise is crucial in guiding the successful design of future anti-cancer therapeutics. Although currently available data indicate that elimination of malignant cells often depends on classical apoptotic pathways (mitochondrial and/or death receptor pathways), the evidence is mounting that alternative apoptotic and non-apoptotic pathways may effectively contribute to tumor cell death. The assumption that every organelle is capable of sensing, amplificating and executing cell death is also a relatively novel and unexplored concept. As recently shown, the secretory pathway can be actively involved in sensing stress stimuli and possibly even initiating and propagating cell death signaling. Experimental evidence indicates that ER and Golgi apparatus can activate both pro-survival (recovery) mechanisms as well as cell suicide programs if the stress-signaling threshold is exceeded. It is thus conceivable that the fragile balance of protein trafficking between various subcellular compartments provides an exceptional therapeutic opportunity. Interestingly, a growing number of reports recognize novel therapeutic targets, including proteins in control of endoplasmic reticulum (ER) and Golgi homeostasis. Further studies are, however, needed to elucidate precise signaling pathways emanating from ER-Golgi compartment. Development of more potent and selective small-molecule drugs that activate ER-Golgi mediated cell demise is also needed. As the interest in the role of ER-Golgi network during cancer cell death has been gaining momentum, we attempt here to critically appraise current status of development of investigational anti-cancer agents that target ER and/or Golgi.
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影响因子：
78.5
作者：
Brown, JM;Attardi, LD
通讯作者：
Attardi, LD
DOI：
10.1073/pnas.89.14.6408
发表时间：
1992-07-15
影响因子：
11.1
作者：
DONALDSON, JG;CASSEL, D;KLAUSNER, RD
通讯作者：
KLAUSNER, RD
DOI：
10.1083/jcb.200208013
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chiu R;Novikov L;Mukherjee S;Shields D
通讯作者：
Shields D
影响因子：
21.3
作者：
Bertolotti, A;Zhang, YH;Ron, D
通讯作者：
Ron, D
影响因子：
21.3
作者：
Boehning, D;Patterson, RL;Snyder, SH
通讯作者：
Snyder, SH