PKC在癌症中的双重作用：促进和抑制癌症

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-08-25 DOI:10.1016/j.genrep.2025.102329

Xu Wang, Jiaming Duan, Chunming Wang

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引用次数: 0

摘要

丝氨酸-苏氨酸激酶蛋白激酶C （PKC）是癌症生物学中的一个关键因子，可分为三个亚家族：常规（cPKC: α, β, γ），新型（nPKC: δ, ε, η, θ）和非典型（aPKC: ζ, λ/ι）。PKC最初被确定为致瘤性磷酯的分子靶点，由于其参与细胞存活、增殖调节、凋亡信号传导和迁移行为等基本细胞过程，PKC已被认为与各种癌症有关。PKC家族包括9个具有不同靶点的基因，使其在癌症中的作用复杂而多方面。在不同类型的癌症中，PKC似乎发挥着不同的作用，在一些癌症中促进癌症，在另一些癌症中抑制癌症，这似乎造成了PKC研究的瓶颈。这篇综述系统地总结了PKC亚型在癌症发病机制中的环境依赖功能，并评估了目前PKC抑制剂和激动剂的治疗概况。通过分析PKC药物开发中持续存在的挑战，提出未来PKC靶向治疗的战略方向，为今后PKC研究提供新的思路。

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PKC in cancer: A dual role in cancer promotion and suppression

The serine-threonine kinase Protein Kinase C (PKC), a critical factor in cancer biology, falls into three subfamilies: conventional (cPKC: α, β, γ), novel (nPKC: δ, ε, η, θ), and atypical (aPKC: ζ, λ/ι). Initially identified as a molecular target of tumorigenic phorbol esters, PKC has since been implicated in various cancers due to its involvement in essential cellular processes like cell survival, proliferative regulation, apoptotic signaling, and migratory behavior. The PKC family comprises nine genes with diverse targets, making its role in cancer complex and multifaceted. In different types of cancer, PKC seems to play a different role, promoting cancer in some cancers, and inhibiting cancer in others, this seems to have caused a bottleneck in PKC research. This review systematically summarized the context-dependent functions of PKC isoforms in cancer pathogenesis and evaluates the therapeutic profiles of current PKC inhibitors and agonists. By analyzing persistent challenges in PKC drug development, we propose strategic directions for future PKC-targeted therapeutics and provide researchers with new ideas for future PKC research.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.