• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

阻断 Axl 信号通路可改善 HPV16E6 介导的宫颈癌肿瘤发生。

Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer.

机构信息

Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Insitute (KAERI), 29 Geumgu-gil, Jeongeup-si, Jeollabuk-do, 580-185, Korea.

School of Biological Sciences and Technology, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 500-757, Korea.

出版信息

Sci Rep. 2017 Jul 18;7(1):5759. doi: 10.1038/s41598-017-05977-8.

DOI:10.1038/s41598-017-05977-8
PMID:28720772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5516033/
Abstract

Axl receptor tyrosine kinase is involved in the tumorigenesis and metastasis of many cancers. Axl expression was markedly higher in human papilloma virus type 16E6 (HPV16E6)-overexpressing HeLa (HE6F) cells and lower in HPV16E6-suppressing CaSki (CE6R) cells than in the controls. SiRNA-mediated knockdown of E6 expression led to increased phosphatase and tensin homolog (PTEN) phosphorylation at Ser380 and attenuated AKT phosphorylation. Expression of membrane-associated guanylate kinase inverted-2 (MAGI-2), an E6-induced degradation target, was induced in E6-siRNA-transfected cells. Moreover, myeloid zinc finger protein 1 (MZF1) binds directly to the Axl promoter in HE6F cells. Axl expression was regulated by HPV16E6-mediated PTEN/AKT signalling pathway, and Axl promoter activity was regulated through MZF1 activation in cervical cancer, which promoted malignancy. Axl silencing suppressed the metastasis of Caski cells and enhanced the susceptibility to NK cell-mediated killing of HE6F cells. In addition, the expression of Axl and MZF1 was highly correlated with clinical stage of cervical cancer and HPV16/18 infection. Taken together, Axl expression was induced by HPV16E6 in cervical cancer cells, suggesting that blockade of Axl signalling might be an effective way to reduce the progression of cervical cancer.

摘要

Axl 受体酪氨酸激酶参与许多癌症的发生和转移。在人乳头瘤病毒 16 型 E6（HPV16E6）过表达的 HeLa（HE6F）细胞中，Axl 的表达明显高于对照，而在 HPV16E6 抑制的 CaSki（CE6R）细胞中则较低。siRNA 介导的 E6 表达下调导致丝氨酸 380 磷酸化的磷酸酶和张力蛋白同源物（PTEN）增加，AKT 磷酸化减弱。E6-siRNA 转染细胞中诱导了膜相关鸟苷酸激酶倒置-2（MAGI-2）的表达，这是一种 E6 诱导的降解靶标。此外，髓系锌指蛋白 1（MZF1）直接结合到 HE6F 细胞中的 Axl 启动子上。Axl 的表达受 HPV16E6 介导的 PTEN/AKT 信号通路调控，Axl 启动子活性通过宫颈癌中 MZF1 的激活来调控，这促进了恶性肿瘤的发生。Axl 沉默抑制了 Caski 细胞的转移，并增强了 NK 细胞对 HE6F 细胞的杀伤敏感性。此外，Axl 和 MZF1 的表达与宫颈癌的临床分期和 HPV16/18 感染高度相关。总之，Axl 的表达是由 HPV16E6 在宫颈癌细胞中诱导的，这表明阻断 Axl 信号可能是减少宫颈癌进展的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/53494f55dbab/41598_2017_5977_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/e555ee91206b/41598_2017_5977_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/a5f6babbfef0/41598_2017_5977_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/9587c89b312a/41598_2017_5977_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/366e30f97f4e/41598_2017_5977_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/87ea04618f31/41598_2017_5977_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/53494f55dbab/41598_2017_5977_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/e555ee91206b/41598_2017_5977_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/a5f6babbfef0/41598_2017_5977_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/9587c89b312a/41598_2017_5977_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/366e30f97f4e/41598_2017_5977_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/87ea04618f31/41598_2017_5977_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d40e/5516033/53494f55dbab/41598_2017_5977_Fig6_HTML.jpg

相似文献

1
Blockade of Axl signaling ameliorates HPV16E6-mediated tumorigenecity of cervical cancer.阻断 Axl 信号通路可改善 HPV16E6 介导的宫颈癌肿瘤发生。
Sci Rep. 2017 Jul 18;7(1):5759. doi: 10.1038/s41598-017-05977-8.
2
Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through Axl gene expression in solid cancer.髓样锌指蛋白 1 通过 Axl 基因表达诱导实体瘤中的迁移、侵袭和体内转移。
Mol Cancer Res. 2010 Feb;8(2):159-69. doi: 10.1158/1541-7786.MCR-09-0326. Epub 2010 Feb 9.
3
Human papillomavirus 16E6 suppresses major histocompatibility complex class I by upregulating lymphotoxin expression in human cervical cancer cells.人乳头瘤病毒 16E6 通过上调人宫颈癌细胞中淋巴毒素的表达来抑制主要组织相容性复合体 I 类分子。
Biochem Biophys Res Commun. 2011 Jun 17;409(4):792-8. doi: 10.1016/j.bbrc.2011.05.090. Epub 2011 May 20.
4
Down-regulation of miR-1246 in cervical cancer tissues and its clinical significance.宫颈癌组织中miR-1246的表达下调及其临床意义。
Gynecol Oncol. 2015 Sep;138(3):683-8. doi: 10.1016/j.ygyno.2015.06.015. Epub 2015 Jun 11.
5
Human Papillomavirus E6/E7 and Long Noncoding RNA TMPOP2 Mutually Upregulated Gene Expression in Cervical Cancer Cells.人乳头瘤病毒 E6/E7 和长非编码 RNA TMPOP2 相互上调宫颈癌细胞的基因表达。
J Virol. 2019 Apr 3;93(8). doi: 10.1128/JVI.01808-18. Print 2019 Apr 15.
6
miR-2861 acts as a tumor suppressor via targeting EGFR/AKT2/CCND1 pathway in cervical cancer induced by human papillomavirus virus 16 E6.miR-2861 通过靶向 HPV16 E6 诱导的宫颈癌中的 EGFR/AKT2/CCND1 通路发挥肿瘤抑制作用。
Sci Rep. 2016 Jul 1;6:28968. doi: 10.1038/srep28968.
7
HPV16 oncoproteins promote cervical cancer invasiveness by upregulating specific matrix metalloproteinases.HPV16 癌蛋白通过上调特定的基质金属蛋白酶促进宫颈癌的侵袭性。
PLoS One. 2013 Aug 13;8(8):e71611. doi: 10.1371/journal.pone.0071611. eCollection 2013.
8
Human papillomavirus 16E6/E7 activates autophagy via Atg9B and LAMP1 in cervical cancer cells.人乳头瘤病毒 16E6/E7 通过 Atg9B 和 LAMP1 在宫颈癌细胞中激活自噬。
Cancer Med. 2019 Aug;8(9):4404-4416. doi: 10.1002/cam4.2351. Epub 2019 Jun 18.
9
HPV16 oncogenes E6 or/and E7 may influence the methylation status of RASSFIA gene promoter region in cervical cancer cell line HT-3.人乳头瘤病毒16型癌基因E6或/和E7可能影响宫颈癌细胞系HT-3中RASSFIA基因启动子区域的甲基化状态。
Oncol Rep. 2017 Apr;37(4):2324-2334. doi: 10.3892/or.2017.5465. Epub 2017 Feb 17.
10
HPV-16/18 E6-induced APOBEC3B expression associates with proliferation of cervical cancer cells and hypomethylation of Cyclin D1.HPV-16/18 E6 诱导的 APOBEC3B 表达与宫颈癌细胞的增殖和细胞周期蛋白 D1 的低甲基化有关。
Mol Carcinog. 2021 May;60(5):313-330. doi: 10.1002/mc.23292. Epub 2021 Feb 25.

引用本文的文献

1
AXL signaling in cancer: from molecular insights to targeted therapies.癌症中的AXL信号传导：从分子洞察到靶向治疗。
Signal Transduct Target Ther. 2025 Feb 10;10(1):37. doi: 10.1038/s41392-024-02121-7.
2
NFX1-123: A potential therapeutic target in cervical cancer.NFX1-123：宫颈癌的潜在治疗靶点。
J Med Virol. 2023 Jun;95(6):e28856. doi: 10.1002/jmv.28856.
3
CABOCOL-01 trial: a single-arm phase II study assessing safety and efficacy of Cabozantinib for advanced or metastatic cervical carcinoma after platinum treatment failure.

本文引用的文献

1
Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer.人乳头瘤病毒：宫颈癌当前及未来的RNA干扰治疗策略
J Clin Med. 2015 May 21;4(5):1126-55. doi: 10.3390/jcm4051126.
2
Up-regulation of FOXM1 by E6 oncoprotein through the MZF1/NKX2-1 axis is required for human papillomavirus-associated tumorigenesis.E6癌蛋白通过MZF1/NKX2-1轴上调FOXM1是人类乳头瘤病毒相关肿瘤发生所必需的。
Neoplasia. 2014 Nov 20;16(11):961-71. doi: 10.1016/j.neo.2014.09.010. eCollection 2014 Nov.
3
The receptor tyrosine kinase Axl in cancer: biological functions and therapeutic implications.
CABOCOL-01 试验：一项单臂 II 期研究，评估卡博替尼治疗铂类治疗失败后的晚期或转移性宫颈癌的安全性和疗效。
BMC Cancer. 2021 Sep 25;21(1):1054. doi: 10.1186/s12885-021-08758-9.
4
HPV 16 E6/E7 Promote the Glucose Uptake of GLUT1 in Lung Cancer Through Downregulation of TXNIP Due to Inhibition of PTEN Phosphorylation.人乳头瘤病毒16型E6/E7通过抑制PTEN磷酸化下调硫氧还蛋白相互作用蛋白（TXNIP），促进肺癌中葡萄糖转运蛋白1（GLUT1）的葡萄糖摄取。
Front Oncol. 2020 Nov 12;10:559543. doi: 10.3389/fonc.2020.559543. eCollection 2020.
5
CTHRC1 as a novel biomarker in the diagnosis of cervical squamous cell carcinoma.CTHRC1作为宫颈鳞状细胞癌诊断中的一种新型生物标志物。
Int J Clin Exp Pathol. 2018 Feb 1;11(2):847-854. eCollection 2018.
6
Role of the zinc finger and SCAN domain-containing transcription factors in cancer.含锌指和SCAN结构域的转录因子在癌症中的作用。
Am J Cancer Res. 2019 May 1;9(5):816-836. eCollection 2019.
7
MZF1 and SCAND1 Reciprocally Regulate Gene Expression in Prostate Cancer.MZF1和SCAND1相互调节前列腺癌中的基因表达。
Cancers (Basel). 2019 Jun 8;11(6):792. doi: 10.3390/cancers11060792.
受体酪氨酸激酶 Axl 在癌症中的作用：生物学功能及治疗意义。
Int J Cancer. 2014 Mar 1;134(5):1024-33. doi: 10.1002/ijc.28246. Epub 2013 Jun 4.
4
Comprehensive analysis of host cellular interactions with human papillomavirus E6 proteins identifies new E6 binding partners and reflects viral diversity.全面分析宿主细胞与人类乳头瘤病毒 E6 蛋白的相互作用，鉴定新的 E6 结合伴侣，并反映病毒多样性。
J Virol. 2012 Dec;86(24):13174-86. doi: 10.1128/JVI.02172-12. Epub 2012 Sep 26.
5
Systematic identification of interactions between host cell proteins and E7 oncoproteins from diverse human papillomaviruses.系统鉴定不同型别人类乳头瘤病毒宿主细胞蛋白与 E7 癌蛋白的相互作用。
Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):E260-7. doi: 10.1073/pnas.1116776109. Epub 2012 Jan 9.
6
Axl-dependent signalling: a clinical update.Axl 依赖性信号转导：临床更新。
Clin Sci (Lond). 2012 Apr;122(8):361-8. doi: 10.1042/CS20110411.
7
Anticancer drugs aimed at E6 and E7 activity in HPV-positive cervical cancer.针对 HPV 阳性宫颈癌中 E6 和 E7 活性的抗癌药物。
Curr Cancer Drug Targets. 2012 Feb;12(2):170-84. doi: 10.2174/156800912799095135.
8
Human papillomavirus 16E6 suppresses major histocompatibility complex class I by upregulating lymphotoxin expression in human cervical cancer cells.人乳头瘤病毒 16E6 通过上调人宫颈癌细胞中淋巴毒素的表达来抑制主要组织相容性复合体 I 类分子。
Biochem Biophys Res Commun. 2011 Jun 17;409(4):792-8. doi: 10.1016/j.bbrc.2011.05.090. Epub 2011 May 20.
9
The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.人乳头瘤病毒 16 型 E6 癌蛋白激活 mTORC1 信号通路并增加蛋白质合成。
J Virol. 2010 Sep;84(18):9398-407. doi: 10.1128/JVI.00974-10. Epub 2010 Jul 14.
10
Myeloid zinc finger 1 induces migration, invasion, and in vivo metastasis through Axl gene expression in solid cancer.髓样锌指蛋白 1 通过 Axl 基因表达诱导实体瘤中的迁移、侵袭和体内转移。
Mol Cancer Res. 2010 Feb;8(2):159-69. doi: 10.1158/1541-7786.MCR-09-0326. Epub 2010 Feb 9.