硼替佐米通过 JNK 激活诱导头颈部鳞状细胞癌细胞自噬。
Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation.
机构信息
Department of Medicine, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
出版信息
Cancer Lett. 2012 Jan 1;314(1):102-7. doi: 10.1016/j.canlet.2011.09.020. Epub 2011 Sep 24.
Abstract
The molecular mechanism of autophagy induction following proteasome inhibition is not fully understood. We report that the proteasome inhibitor bortezomib potently induces autophagy in head and neck squamous cell carcinoma (HNSCC) cells, as demonstrated by autophagosome formation and induction of complete autophagic flux. Bortezomib treatment led to phosphorylation/activation of jun N-terminal kinase (JNK) enzymes and JNK-dependent phosphorylation of Bcl-2 on serine 70. Pharmacologic inhibition of JNK, but not p38 MAPK, dramatically inhibited bortezomib induction of autophagy regulatory proteins and autophagosome formation. These results demonstrate a key requirement for JNK signaling in the activation of autophagy by bortezomib.
摘要
蛋白酶体抑制后自噬诱导的分子机制尚不完全清楚。我们报告称，蛋白酶体抑制剂硼替佐米可强烈诱导头颈部鳞状细胞癌（HNSCC）细胞发生自噬，这可通过自噬体形成和完全自噬流的诱导来证明。硼替佐米处理导致 jun N 末端激酶（JNK）酶的磷酸化/激活，以及 Bcl-2 丝氨酸 70 上的 JNK 依赖性磷酸化。JNK 而不是 p38 MAPK 的药理学抑制显著抑制硼替佐米诱导的自噬调节蛋白和自噬体形成。这些结果表明 JNK 信号在硼替佐米激活自噬中起关键作用。
相似文献
1
Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation.硼替佐米通过 JNK 激活诱导头颈部鳞状细胞癌细胞自噬。
Cancer Lett. 2012 Jan 1;314(1):102-7. doi: 10.1016/j.canlet.2011.09.020. Epub 2011 Sep 24.
2
Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells.硼替佐米通过上调Bim和Bik诱导细胞凋亡，并在杀死头颈部鳞状细胞癌细胞方面与顺铂协同作用。
Mol Cancer Ther. 2008 Jun;7(6):1647-55. doi: 10.1158/1535-7163.MCT-07-2444.
3
Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells.蛋白酶体抑制剂PS-341通过诱导头颈部鳞状细胞癌细胞内质网应激反应性氧物种来诱导细胞凋亡。
Mol Cell Biol. 2004 Nov;24(22):9695-704. doi: 10.1128/MCB.24.22.9695-9704.2004.
4
The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4.下一代蛋白酶体抑制剂卡非佐米和奥普佐米通过诱导未折叠蛋白反应和 ATF4 激活促生存自噬。
Autophagy. 2012 Dec;8(12):1873-4. doi: 10.4161/auto.22185. Epub 2012 Sep 20.
5
The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor Bortezomib.在响应蛋白酶体抑制剂硼替佐米而发生凋亡的人白血病细胞中，MAPK信号传导与活性氧生成之间的层级关系。
Exp Cell Res. 2004 May 1;295(2):555-66. doi: 10.1016/j.yexcr.2004.02.001.
6
Bortezomib enhances cancer cell death by blocking the autophagic flux through stimulating ERK phosphorylation.硼替佐米通过刺激细胞外信号调节激酶（ERK）磷酸化来阻断自噬流，从而增强癌细胞死亡。
Cell Death Dis. 2014 Nov 6;5(11):e1510. doi: 10.1038/cddis.2014.468.
7
Nuclear factor-kappaB p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101.核因子-κB p65小干扰RNA或蛋白酶体抑制剂硼替佐米使头颈部鳞状细胞癌对经典组蛋白去乙酰化酶抑制剂和新型组蛋白去乙酰化酶抑制剂PXD101敏感。
Mol Cancer Ther. 2007 Jan;6(1):37-50. doi: 10.1158/1535-7163.MCT-05-0285.
8
Bcl-2 antagonists interact synergistically with bortezomib in DLBCL cells in association with JNK activation and induction of ER stress.Bcl-2 拮抗剂与硼替佐米在弥漫性大 B 细胞淋巴瘤细胞中协同作用，与 JNK 激活和内质网应激诱导有关。
Cancer Biol Ther. 2009 May;8(9):808-19. doi: 10.4161/cbt.8.9.8131. Epub 2009 May 8.
9
PS-341 and histone deacetylase inhibitor synergistically induce apoptosis in head and neck squamous cell carcinoma cells.PS-341 和组蛋白去乙酰化酶抑制剂协同诱导头颈部鳞状细胞癌细胞凋亡。
Mol Cancer Ther. 2010 Jul;9(7):1977-84. doi: 10.1158/1535-7163.MCT-10-0141. Epub 2010 Jun 22.
10
Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway in vitro.硼替佐米在体外通过丝裂原活化蛋白激酶途径诱导骨肉瘤细胞凋亡和自噬。
J Int Med Res. 2013 Oct;41(5):1505-19. doi: 10.1177/0300060513490618. Epub 2013 Aug 23.
引用本文的文献
1
Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.泛素化调节癌症中的自噬：简单的修饰，有前途的靶点。
J Transl Med. 2024 Oct 31;22(1):985. doi: 10.1186/s12967-024-05565-1.
2
Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress-Mitochondrial Apoptotic and Autophagic Signaling Pathway.Stellettin B 通过内质网应激-线粒体凋亡和自噬信号通路诱导口腔癌细胞死亡。
Int J Mol Sci. 2022 Aug 8;23(15):8813. doi: 10.3390/ijms23158813.
3
circ_0000045 promotes proliferation, migration, and invasion of head and neck squamous cell carcinomas via regulating HSP70 and MAPK pathway.circ_0000045 通过调节 HSP70 和 MAPK 通路促进头颈部鳞状细胞癌的增殖、迁移和侵袭。
BMC Cancer. 2022 Jul 20;22(1):799. doi: 10.1186/s12885-022-09880-y.
4
Progress on the Application of Bortezomib and Bortezomib-Based Nanoformulations.硼替佐米及其基于纳米制剂的应用进展。
Biomolecules. 2021 Dec 30;12(1):51. doi: 10.3390/biom12010051.
5
Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.心脏糖苷作为潜在药物的出现：癌症治疗的当前和未来范围。
Biomolecules. 2021 Aug 25;11(9):1275. doi: 10.3390/biom11091275.
6
Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.硼替佐米对蛋白酶体的抑制作用类似于减少头颈部癌细胞的生长，并增加肿瘤浸润免疫细胞。
Sci Rep. 2021 Sep 24;11(1):19051. doi: 10.1038/s41598-021-98450-6.
7
Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection.硼替佐米对全身慢性活动性 EBV 感染的抗肿瘤和抗炎作用。
Blood Adv. 2021 Apr 13;5(7):1805-1815. doi: 10.1182/bloodadvances.2020002417.
8
Role of Autophagy in Cancer Cell Response to Nucleolar and Endoplasmic Reticulum Stress.自噬在癌细胞应对核仁与内质网应激中的作用。
Int J Mol Sci. 2020 Oct 4;21(19):7334. doi: 10.3390/ijms21197334.
9
The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.蛋白酶体作为一个具有多种治疗潜力的可药物靶标：有切与非切的两面性。
Pharmacol Ther. 2020 Sep;213:107579. doi: 10.1016/j.pharmthera.2020.107579. Epub 2020 May 19.
10
The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages.口腔癌中的 p38/MKP-1 信号轴：肿瘤相关巨噬细胞的影响。
Oral Oncol. 2020 Apr;103:104591. doi: 10.1016/j.oraloncology.2020.104591. Epub 2020 Feb 10.
本文引用的文献
1
Regulation of autophagy by ATF4 in response to severe hypoxia.ATF4 调控自噬以应对严重缺氧。
Oncogene. 2010 Aug 5;29(31):4424-35. doi: 10.1038/onc.2010.191. Epub 2010 May 31.
2
Bortezomib induces autophagic death in proliferating human endothelial cells.硼替佐米诱导增殖的人内皮细胞发生自噬性死亡。
Exp Cell Res. 2010 Apr 1;316(6):1010-8. doi: 10.1016/j.yexcr.2009.11.005. Epub 2009 Nov 13.
3
Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells.蛋白酶体抑制剂通过诱导自噬作为一种细胞保护应答激活人前列腺癌细胞。
Oncogene. 2010 Jan 21;29(3):451-62. doi: 10.1038/onc.2009.343. Epub 2009 Nov 2.
4
c-Jun NH2-terminal kinase activation is essential for DRAM-dependent induction of autophagy and apoptosis in 2-methoxyestradiol-treated Ewing sarcoma cells.c-Jun氨基末端激酶激活对于2-甲氧基雌二醇处理的尤因肉瘤细胞中DRAM依赖的自噬和凋亡诱导至关重要。
Cancer Res. 2009 Sep 1;69(17):6924-31. doi: 10.1158/0008-5472.CAN-09-1270. Epub 2009 Aug 25.
5
Bortezomib up-regulates activated signal transducer and activator of transcription-3 and synergizes with inhibitors of signal transducer and activator of transcription-3 to promote head and neck squamous cell carcinoma cell death.硼替佐米上调激活的信号转导子和转录激活子 3 并与信号转导子和转录激活子 3 的抑制剂协同作用，促进头颈部鳞状细胞癌细胞死亡。
Mol Cancer Ther. 2009 Aug;8(8):2211-20. doi: 10.1158/1535-7163.MCT-09-0327. Epub 2009 Jul 28.
6
Oncogenic transformation confers a selective susceptibility to the combined suppression of the proteasome and autophagy.致癌转化赋予了对蛋白酶体和自噬联合抑制的选择性易感性。
Mol Cancer Ther. 2009 Jul;8(7):2036-45. doi: 10.1158/1535-7163.MCT-08-1169. Epub 2009 Jul 7.
7
Effect of autophagy on multiple myeloma cell viability.自噬对多发性骨髓瘤细胞活力的影响。
Mol Cancer Ther. 2009 Jul;8(7):1974-84. doi: 10.1158/1535-7163.MCT-08-1177. Epub 2009 Jun 9.
8
Cancer statistics, 2009.2009年癌症统计数据。
CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.
9
Upregulation of Beclin-1 expression and phosphorylation of Bcl-2 and p53 are involved in the JNK-mediated autophagic cell death.Beclin-1表达的上调以及Bcl-2和p53的磷酸化参与了JNK介导的自噬性细胞死亡。
Biochem Biophys Res Commun. 2009 May 15;382(4):726-9. doi: 10.1016/j.bbrc.2009.03.095. Epub 2009 Mar 24.
10
The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells.c-Jun氨基末端激酶介导的Beclin 1表达在抗癌药物诱导癌细胞自噬过程中的关键作用。
Oncogene. 2009 Feb 12;28(6):886-98. doi: 10.1038/onc.2008.441. Epub 2008 Dec 8.
Zotero 插件