Abstract
Simple SummaryThe protein kinase C (PKC) family belongs to serine-threonine kinases and consists of several subtypes. Increasing evidence suggests that PKCs are critical players in carcinogenesis. Interestingly, PKCs exert both promotive and suppressive effects on tumor cell growth and metastasis, which have attracted immense attention. Herein, we systematically review the current advances in the structure, regulation and biological functions of PKCs, especially the relationship of PKCs with anti-cancer therapy-induced cell death, including the current knowledge of PKCs function in tumor metabolism and microenvironment. Moreover, we discuss the potential role of PKCs as a target for therapeutic intervention in cancer from basic research and clinical trials.Protein kinase C (PKC) isoforms, a group of serine-threonine kinases, are important regulators in carcinogenesis. Numerous studies have demonstrated that PKC isoforms exert both positive and negative effects on cancer cell demise. In this review, we systematically summarize the current findings on the architecture, activity regulation and biological functions of PKCs, especially their relationship with anti-cancer therapy-induced cell death. Additionally, we elaborate on current knowledge of the effects of PKCs on tumor metabolism and microenvironment, which have gained increasing attention in oncology-related areas. Furthermore, we underscore the basic experimental and clinical implications of PKCs as a target for cancer therapy to evaluate their therapeutic benefits and potential applications.
Highlights
Protein kinase C (PKC) isoenzymes are a prototypical class of serine/threonine kinases that are conserved throughout evolution and widely expressed in almost all cell types
We focus on the regulatory activities of PKC isoforms and discuss their involvement in cancer progression
It is obvious that PKC isoforms are involved in cancer progression and represent important targets for cancer therapy
Summary
Protein kinase C (PKC) isoenzymes are a prototypical class of serine/threonine kinases that are conserved throughout evolution and widely expressed in almost all cell types. They consist of domain permutations in their N-terminal regulatory regions linked by variable sequences to a highly conserved C-terminal kinase domain. The PKC signaling pathway has critical roles in regulating gene expression, as well as cell proliferation, differentiation, migration, survival and death. Recent scientific breakthroughs and technological advancements have improved our understanding of the functional roles of PKCs in cancer development and progression. We focus on the regulatory activities of PKC isoforms and discuss their involvement in cancer progression. We provide a summary of clinical trials with PKC inhibitors in cancers and highlight the latest development of PKCs as targeted anti-cancer therapies
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