Protein kinase C as a tumor suppressor.
Protein kinase C as a tumor suppressor.
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DOI：
10.1016/j.semcancer.2017.04.017
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发表时间：
2018-03
影响因子：
14.5
通讯作者：
Newton AC
中科院分区：
文献类型：
--
作者：
Newton AC
蛋白激酶C（PKC）历来被认为是一种癌蛋白。这在很大程度上源于20世纪80年代初的发现，即PKC直接被促进肿瘤的佛波酯激活。然而，在癌症治疗中使用PKC抑制剂的30年临床试验不仅失败了，而且在某些情况下恶化了患者的预后。为什么靶向癌症中的PKC无法成功治疗？最近的研究着眼于疾病的洞察力提供了一个解释：癌症相关的PKC突变通常是功能丧失（LOF），支持作为肿瘤抑制因子的意外功能。而且，与癌症中的LOF突变相比，增强某些PKC同工酶活性的种系突变与退行性疾病如阿尔茨海默病有关。这篇综述提供了一个背景上的不同机制，确保PKC是活跃的，只有在适当的时间，地点和所需的时间，并总结了最近的研究结果收敛于一个范式逆转：PKC家族成员一般功能抑制，而不是促进，生存信号。
Protein kinase C (PKC) has historically been considered an oncoprotein. This stems in large part from the discovery in the early 1980s that PKC is directly activated by tumor-promoting phorbol esters. Yet three decades of clinical trials using PKC inhibitors in cancer therapies not only failed, but in some cases worsened patient outcome. Why has targeting PKC in cancer eluded successful therapies? Recent studies looking at the disease for insight provide an explanation: cancer-associated mutations in PKC are generally loss-of-function (LOF), supporting an unexpected function as tumor suppressors. And, contrasting with LOF mutations in cancer, germline mutations that enhance the activity of some PKC isozymes are associated with degenerative diseases such as Alzheimer's disease. This review provides a background on the diverse mechanisms that ensure PKC is only active when, where, and for the appropriate duration needed and summarizes recent findings converging on a paradigm reversal: PKC family members generally function by suppressing, rather than promoting, survival signaling.
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影响因子：
64.5
作者：
Antal CE;Hudson AM;Kang E;Zanca C;Wirth C;Stephenson NL;Trotter EW;Gallegos LL;Miller CJ;Furnari FB;Hunter T;Brognard J;Newton AC
通讯作者：
Newton AC
影响因子：
64.5
作者：
Creixell P;Schoof EM;Simpson CD;Longden J;Miller CJ;Lou HJ;Perryman L;Cox TR;Zivanovic N;Palmeri A;Wesolowska-Andersen A;Helmer-Citterich M;Ferkinghoff-Borg J;Itamochi H;Bodenmiller B;Erler JT;Turk BE;Linding R
通讯作者：
Linding R
影响因子：
--
作者：
Bernatsky, S;Boivin, JF;Clarke, A
通讯作者：
Clarke, A
影响因子：
11.2
作者：
Barcelo, Carles;Paco, Noelia;Agell, Neus
通讯作者：
Agell, Neus
影响因子：
5.8
作者：
BLUMBERG, PM;JAKEN, S;YEH, E
通讯作者：
YEH, E