Atypical protein kinase Cι as a human oncogene and therapeutic target.
Atypical protein kinase Cι as a human oncogene and therapeutic target.
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非典型蛋白激酶Cι作为人类癌基因和治疗靶标。
DOI：
10.1016/j.bcp.2013.10.023
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发表时间：
2014-03-01
影响因子：
5.8
通讯作者：
Fields, Alan P.
中科院分区：
文献类型：
--
作者：
Parker, Peter J.;Justilien, Verline;Riou, Philippe;Linch, Mark;Fields, Alan P.
关键词：
蛋白激酶抑制剂代表了一类主要的靶向治疗药物，对癌症和其他疾病适应症的治疗产生了积极影响。蛋白激酶C（PKC）家族成员是用于进一步治疗开发的有前景的激酶靶标之一，PKC是调节多种细胞功能（包括增殖、细胞周期、分化、存活、细胞迁移和极性）的许多信号传导途径的中心组分。单个PKC同工酶的遗传操作已经证明它们通常实现不同的、非冗余的细胞功能。11 PKC成员参与不同的细胞内信号传导途径反映了对不同的细胞外刺激、细胞内定位、组织分布、磷酸化状态和分子间相互作用的反应。PKC活性、定位、磷酸化和/或表达在人类肿瘤中经常改变，并且PKC同工酶已经涉及转化的各个方面，包括不受控制的增殖、迁移、侵袭、转移、血管生成和对细胞凋亡的抗性。尽管PKC同工酶与癌症之间存在强相关性，但迄今为止，仅非典型的PKC 1 ota已显示出作为真正的致癌基因起作用，因此是癌症治疗的特别有吸引力的治疗靶标。在这篇综述中，我们讨论了PKCiota在转化中的作用，并描述了基于机制的方法来治疗癌症中的致癌PKCiota信号传导。
Protein kinase inhibitors represent a major class of targeted therapeutics that has made a positive impact on treatment of cancer and other disease indications. Among the promising kinase targets for further therapeutic development are members of the Protein Kinase C (PKC) family.The PKCs are central components of many signaling pathways that regulate diverse cellular functions including proliferation, cell cycle, differentiation, survival, cell migration, and polarity. Genetic manipulation of individual PKC isozymes has demonstrated that they often fulfill distinct, nonredundant cellular functions.11 Participation of PKC members in different intracellular signaling pathways reflects responses to varying extracellular stimuli, intracellular localization, tissue distribution, phosphorylation status, and intermolecular interactions. PKC activity, localization, phosphorylation, and/or expression are often altered in human tumors, and PKC isozymes have been implicated in various aspects of transformation, including uncontrolled proliferation, migration, invasion, metastasis, angiogenesis, and resistance to apoptosis. Despite the strong relationship between PKC isozymes and cancer, to date only atypical PKCiota has been shown to function as a bona fide oncogene, and as such is a particularly attractive therapeutic target for cancer treatment. In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer.
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影响因子：
8
作者：
Baldwin, R. M.;Parolin, D. A. E.;Lorimer, I. A. J.
通讯作者：
Lorimer, I. A. J.
影响因子：
5.3
作者：
Gunaratne, Adrian;Thai, Boun L.;Di Guglielmo, Gianni M.
通讯作者：
Di Guglielmo, Gianni M.
DOI：
10.1073/pnas.0505641102
发表时间：
2005-08-30
影响因子：
11.1
作者：
Eder, AM;Sui, XM;Mills, GB
通讯作者：
Mills, GB
影响因子：
3.5
作者：
Gschwendt, M;Dieterich, S;Johannes, FJ
通讯作者：
Johannes, FJ
DOI：
10.1158/1078-0432.ccr-08-2459
发表时间：
2009-03-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Erdogan E;Klee EW;Thompson EA;Fields AP
通讯作者：
Fields AP