非典型蛋白激酶 C 在癌症中的双重作用。
The Dual Roles of the Atypical Protein Kinase Cs in Cancer.
机构信息
Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Cancer Cell. 2019 Sep 16;36(3):218-235. doi: 10.1016/j.ccell.2019.07.010. Epub 2019 Aug 29.
Abstract
Atypical protein kinase C (aPKC) isozymes, PKCλ/ι and PKCζ, are now considered fundamental regulators of tumorigenesis. However, the specific separation of functions that determine their different roles in cancer is still being unraveled. Both aPKCs have pleiotropic context-dependent functions that can translate into tumor-promoter or -suppressive functions. Here, we review early and more recent literature to discuss how the different tumor types, and their microenvironments, might account for the selective signaling of each aPKC isotype. This is of clinical relevance because a better understanding of the roles of these kinases is essential for the design of new anti-cancer treatments.
摘要
非典型蛋白激酶 C（aPKC）同工酶 PKCλ/ι 和 PKCζ 现在被认为是肿瘤发生的基本调节因子。然而，决定它们在癌症中不同作用的具体功能分离仍在研究中。两种 aPKC 都具有多效性、上下文依赖性的功能，可以转化为促进肿瘤或抑制肿瘤的功能。在这里，我们回顾了早期和最近的文献，讨论了不同的肿瘤类型及其微环境如何解释每种 aPKC 同工型的选择性信号传递。这具有临床相关性，因为更好地了解这些激酶的作用对于设计新的抗癌治疗方法至关重要。
相似文献
1
The Dual Roles of the Atypical Protein Kinase Cs in Cancer.非典型蛋白激酶 C 在癌症中的双重作用。
Cancer Cell. 2019 Sep 16;36(3):218-235. doi: 10.1016/j.ccell.2019.07.010. Epub 2019 Aug 29.
2
Protein kinase Cλ/ι in cancer: a contextual balance of time and signals.蛋白激酶 Cλ/ι 在癌症中的作用：时间和信号的上下文平衡。
Trends Cell Biol. 2022 Dec;32(12):1023-1034. doi: 10.1016/j.tcb.2022.04.002. Epub 2022 Apr 29.
3
Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance.肠上皮中非典型蛋白激酶 C 基因的同时缺失通过损害免疫监视导致锯齿状肠道肿瘤。
Immunity. 2018 Dec 18;49(6):1132-1147.e7. doi: 10.1016/j.immuni.2018.09.013. Epub 2018 Dec 11.
4
A small molecule inhibitor of atypical protein kinase C signaling inhibits pancreatic cancer cell transformed growth and invasion.一种非典型蛋白激酶C信号通路的小分子抑制剂可抑制胰腺癌细胞的转化生长和侵袭。
Oncotarget. 2015 Jun 20;6(17):15297-310. doi: 10.18632/oncotarget.3812.
5
Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade.非典型蛋白激酶 C-ι 的抑制可通过下调 NF-κB 信号级联有效降低前列腺癌细胞的恶性程度。
Int J Oncol. 2018 Nov;53(5):1836-1846. doi: 10.3892/ijo.2018.4542. Epub 2018 Aug 28.
6
Protein kinase C lambda/iota (PKClambda/iota): a PKC isotype essential for the development of multicellular organisms.蛋白激酶Cλ/ι（PKCλ/ι）：一种对多细胞生物发育至关重要的蛋白激酶C亚型。
J Biochem. 2003 Jan;133(1):9-16. doi: 10.1093/jb/mvg018.
7
Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis.两种新型非典型蛋白激酶 C 抑制剂 ACPD 和 DNDA 可有效抑制转移性黑色素瘤的细胞增殖和上皮间质转化，同时诱导细胞凋亡。
Int J Oncol. 2017 Nov;51(5):1370-1382. doi: 10.3892/ijo.2017.4131. Epub 2017 Sep 22.
8
Editorial.社论。
Adv Biol Regul. 2021 May;80:100770. doi: 10.1016/j.jbior.2020.100770. Epub 2020 Nov 26.
9
Atypical protein kinase Cι as a human oncogene and therapeutic target.非典型蛋白激酶 Cι 作为人类致癌基因和治疗靶点。
Biochem Pharmacol. 2014 Mar 1;88(1):1-11. doi: 10.1016/j.bcp.2013.10.023. Epub 2013 Nov 11.
10
Pleckstrin Homology (PH) Domain Leucine-rich Repeat Protein Phosphatase Controls Cell Polarity by Negatively Regulating the Activity of Atypical Protein Kinase C.普列克底物蛋白同源（PH）结构域富含亮氨酸重复序列蛋白磷酸酶通过负调控非典型蛋白激酶C的活性来控制细胞极性。
J Biol Chem. 2016 Nov 25;291(48):25167-25178. doi: 10.1074/jbc.M116.740639. Epub 2016 Oct 19.
引用本文的文献
1
Protein post-translational modifications in serine synthetic pathway: functions and molecular mechanisms.丝氨酸合成途径中的蛋白质翻译后修饰：功能与分子机制
Cell Commun Signal. 2025 Jul 1;23(1):311. doi: 10.1186/s12964-025-02327-4.
2
Polarity protein Par6 facilitates the processive phosphorylation of Lgl via a dynamic interaction with aPKC.极性蛋白Par6通过与非典型蛋白激酶C（aPKC）的动态相互作用促进Lgl的持续性磷酸化。
Commun Biol. 2025 Jul 1;8(1):967. doi: 10.1038/s42003-025-08401-4.
3
High Expression of And Is Associated With Poor Prognosis in Luminal B Breast Cancer.和的高表达与管腔B型乳腺癌的不良预后相关。
Cancer Genomics Proteomics. 2025 Jun 26;22(4):538-556. doi: 10.21873/cgp.20520.
4
Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression.极性基因PARD6B通过增加MYC表达促进结直肠癌的肿瘤生长。
Cancer Sci. 2025 Sep;116(9):2507-2522. doi: 10.1111/cas.70119. Epub 2025 Jun 18.
5
YAP/TEAD4/SP1-induced VISTA expression as a tumor cell-intrinsic mechanism of immunosuppression in colorectal cancer.YAP/TEAD4/SP1诱导的VISTA表达作为结直肠癌免疫抑制的肿瘤细胞内在机制。
Cell Death Differ. 2025 May;32(5):911-925. doi: 10.1038/s41418-025-01446-2. Epub 2025 Jan 28.
6
Rare variants in cause Van der Woude syndrome and other features of peridermopathy.[基因]中的罕见变异会导致范德伍德综合征和其他皮肤周皮病特征。 （注：原文中“in”后面缺少具体基因名称等关键信息，翻译只能做到尽量符合原文结构，实际意思可能不完整）
medRxiv. 2025 Jan 17:2025.01.17.25320742. doi: 10.1101/2025.01.17.25320742.
7
Cell polarity proteins promote macropinocytosis in response to metabolic stress.细胞极性蛋白在代谢应激反应中促进巨胞饮作用。
Nat Commun. 2024 Dec 3;15(1):10541. doi: 10.1038/s41467-024-54788-9.
8
PKC inhibitors promote breast cancer immune evasion by maintaining PD-L1 stability.蛋白激酶C抑制剂通过维持程序性死亡受体配体1的稳定性促进乳腺癌免疫逃逸。
Acta Pharm Sin B. 2024 Oct;14(10):4378-4395. doi: 10.1016/j.apsb.2024.08.003. Epub 2024 Aug 8.
9
Genetic polymorphism in untranslated regions of PRKCZ influences mRNA structure, stability and binding sites.PRKCZ 非翻译区的遗传多态性影响 mRNA 结构、稳定性和结合位点。
BMC Cancer. 2024 Sep 13;24(1):1147. doi: 10.1186/s12885-024-12900-8.
10
Epithelial aPKC deficiency leads to stem cell loss preceding metaplasia in colorectal cancer initiation.上皮非典型蛋白激酶C缺乏导致结直肠癌起始过程中化生之前的干细胞丢失。
Dev Cell. 2024 Aug 5;59(15):1972-1987.e8. doi: 10.1016/j.devcel.2024.05.001. Epub 2024 May 29.
本文引用的文献
1
Protein Kinase Cι and Wnt/β-Catenin Signaling: Alternative Pathways to Kras/Trp53-Driven Lung Adenocarcinoma.蛋白激酶 Cι 和 Wnt/β-连环蛋白信号通路：Kras/Trp53 驱动的肺腺癌的另一种途径。
Cancer Cell. 2019 Aug 12;36(2):156-167.e7. doi: 10.1016/j.ccell.2019.07.002. Epub 2019 Aug 1.
2
Increased Serine and One-Carbon Pathway Metabolism by PKCλ/ι Deficiency Promotes Neuroendocrine Prostate Cancer.PKCλ/ι 缺失导致丝氨酸和一碳代谢途径增加，促进神经内分泌前列腺癌。
Cancer Cell. 2019 Mar 18;35(3):385-400.e9. doi: 10.1016/j.ccell.2019.01.018. Epub 2019 Feb 28.
3
Apical-basal polarity inhibits epithelial-mesenchymal transition and tumour metastasis by PAR-complex-mediated SNAI1 degradation.顶端-基底极性通过 PAR 复合物介导的 SNAI1 降解抑制上皮-间充质转化和肿瘤转移。
Nat Cell Biol. 2019 Mar;21(3):359-371. doi: 10.1038/s41556-019-0291-8. Epub 2019 Feb 25.
4
PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model.PKCζ 促进前列腺癌细胞在小鼠异种移植模型中的淋巴转移扩散。
Oncogene. 2019 May;38(22):4215-4231. doi: 10.1038/s41388-019-0722-9. Epub 2019 Jan 31.
5
The signaling axis atypical protein kinase C λ/ι-Satb2 mediates leukemic transformation of B-cell progenitors.非典型蛋白激酶 C λ/ι-Satb2 信号轴介导 B 细胞祖细胞的白血病转化。
Nat Commun. 2019 Jan 4;10(1):46. doi: 10.1038/s41467-018-07846-y.
6
mTOR as a central hub of nutrient signalling and cell growth.mTOR 作为营养信号和细胞生长的中央枢纽。
Nat Cell Biol. 2019 Jan;21(1):63-71. doi: 10.1038/s41556-018-0205-1. Epub 2019 Jan 2.
7
Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance.肠上皮中非典型蛋白激酶 C 基因的同时缺失通过损害免疫监视导致锯齿状肠道肿瘤。
Immunity. 2018 Dec 18;49(6):1132-1147.e7. doi: 10.1016/j.immuni.2018.09.013. Epub 2018 Dec 11.
8
LAP2 Proteins Chaperone GLI1 Movement between the Lamina and Chromatin to Regulate Transcription.LAP2 蛋白作为分子伴侣介导 GLI1 在核膜和染色质之间的运动，从而调节转录。
Cell. 2019 Jan 10;176(1-2):198-212.e15. doi: 10.1016/j.cell.2018.10.054. Epub 2018 Nov 29.
9
Comparison of the Kinase Profile of Midostaurin (Rydapt) with That of Its Predominant Metabolites and the Potential Relevance of Some Newly Identified Targets to Leukemia Therapy.米哚妥林（瑞达法特）与其主要代谢物的激酶谱比较以及一些新发现靶点与白血病治疗的潜在相关性。
Biochemistry. 2018 Sep 25;57(38):5576-5590. doi: 10.1021/acs.biochem.8b00727. Epub 2018 Sep 13.
10
aPKC: the Kinase that Phosphorylates Cell Polarity.非典型蛋白激酶C：使细胞极性磷酸化的激酶。
F1000Res. 2018 Jun 25;7. doi: 10.12688/f1000research.14427.1. eCollection 2018.
Zotero 插件