Protein kinase Cι:: Human oncogene, prognostic marker and therapeutic target

被引:102
作者
Fields, Alan P. [1 ]
Regala, Roderick P. [1 ]
机构
[1] Mayo Clin, Ctr Comprehens Canc, Dept Canc Biol, Jacksonville, FL 32224 USA
关键词
atypical protein kinase C; Par6; Phox/Bem1; domain; cancer signaling; cell polarity; hyperproliferation; invasion and metastasis; mechanism-based therapeutics; aurothiomalate;
D O I
10.1016/j.phrs.2007.04.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The protein kinase C (PKC) family of serine/threonine kinases has been the subject of intensive study in the field of cancer since their initial discovery as major cellular receptors for the tumor promoting phorbol esters nearly 30 years ago. However, despite these efforts, the search for a direct genetic link between members of the PKC family and human cancer has yielded only circumstantial evidence that any PKC isozyme is a true cancer gene. This situation changed in the past year with the discovery that atypical protein kinase C iota (PKC iota) is a bonafide human oncogene. PKC iota is required for the transformed growth of human cancer cells and the PKC iota gene is the target of tumor-specific gene amplification in multiple forms of human cancer. PKC iota participates in multiple aspects of the transformed phenotype of human cancer cells including transformed growth, invasion and survival. Herein, we review pertinent aspects of atypical PKC structure, function and regulation that relate to the role of these enzymes in oncogenesis. We discuss the evidence that PKC iota is a human oncogene, review mechanisms controlling PKC iota expression in human cancers, and describe the molecular details of PKC iota-mediated oncogenic signaling. We conclude with a discussion of how oncogenic PKC iota signaling has been successfully targeted to identify a novel, mechanism-based therapeutic drug currently entering clinical trials for treatment of human lung cancer. Throughout, we identify key unanswered questions and exciting future avenues of investigation regarding this important oncogenic molecule. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:487 / 497
页数:11
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