• 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

乙酰肝素酶通过激活p38/基质金属蛋白酶-1轴促进结肠癌细胞的肿瘤生长和肝转移。

Heparanase Promotes Tumor Growth and Liver Metastasis of Colorectal Cancer Cells by Activating the p38/MMP1 Axis.

作者信息

Liu Xue, Zhou Zhi-Hang, Li Wen, Zhang Shi-Kun, Li Jing, Zhou Ming-Ju, Song Jin-Wen

机构信息

Department of Pathology, College of Basic Medicine, Jining Medical University, Jining, China.

Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Front Oncol. 2019 Apr 2;9:216. doi: 10.3389/fonc.2019.00216. eCollection 2019.

DOI:10.3389/fonc.2019.00216
PMID:31001480
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6454005/
Abstract

Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. In this study, we examined the expression of HPSE in different colorectal cancer (CRC) cell lines. Gene manipulation was applied to reveal the effect of HPSE on proliferation, invasion, and metastasis of CRC. Knockdown of HPSE resulted in decreased cell proliferation , whereas overexpression of HPSE resulted in the opposite phenomenon. Consistently, data showed that knockdown of HPSE suppressed tumor growth of CRC. Furthermore, knockdown of HPSE inhibited invasion and liver metastasis and . RNA-sequencing analysis was performed upon knockdown of HPSE, and several pathways were identified that are closely associated with invasion and metastasis. In addition, HPSE is positively correlated with MMP1 expression in CRC, and HPSE regulates MMP1 expression via p38 MAPK signaling pathway. In conclusion, our data demonstrate that HPSE knockdown attenuated tumor growth and liver metastasis in CRC, implying that HPSE might serve as a potential therapeutic target in the treatment of CRC.

摘要

乙酰肝素酶（HPSE）是唯一已知的负责切割硫酸乙酰肝素的哺乳动物内切糖苷酶，是一种影响癌细胞多种恶性行为的多面蛋白。在本研究中，我们检测了HPSE在不同结直肠癌（CRC）细胞系中的表达。应用基因操作来揭示HPSE对CRC增殖、侵袭和转移的影响。敲低HPSE导致细胞增殖减少，而HPSE过表达则导致相反的现象。一致地，数据显示敲低HPSE可抑制CRC的肿瘤生长。此外，敲低HPSE可抑制侵袭和肝转移。在敲低HPSE后进行了RNA测序分析，并确定了几个与侵袭和转移密切相关的途径。此外，HPSE与CRC中MMP1的表达呈正相关，并且HPSE通过p38 MAPK信号通路调节MMP1的表达。总之，我们的数据表明，敲低HPSE可减弱CRC的肿瘤生长和肝转移，这意味着HPSE可能作为治疗CRC的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/ce2d78ac10a7/fonc-09-00216-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/c7c3b832488c/fonc-09-00216-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/5a81bd6ca38f/fonc-09-00216-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/808bd271ec46/fonc-09-00216-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/918cda8020e6/fonc-09-00216-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/697b370f1ff2/fonc-09-00216-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/d496c123d0a6/fonc-09-00216-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/ce2d78ac10a7/fonc-09-00216-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/c7c3b832488c/fonc-09-00216-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/5a81bd6ca38f/fonc-09-00216-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/808bd271ec46/fonc-09-00216-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/918cda8020e6/fonc-09-00216-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/697b370f1ff2/fonc-09-00216-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/d496c123d0a6/fonc-09-00216-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a2d/6454005/ce2d78ac10a7/fonc-09-00216-g0007.jpg

相似文献

1
Heparanase Promotes Tumor Growth and Liver Metastasis of Colorectal Cancer Cells by Activating the p38/MMP1 Axis.乙酰肝素酶通过激活p38/基质金属蛋白酶-1轴促进结肠癌细胞的肿瘤生长和肝转移。
Front Oncol. 2019 Apr 2;9:216. doi: 10.3389/fonc.2019.00216. eCollection 2019.
2
miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase.微小RNA-558通过激活乙酰肝素酶的转录促进神经母细胞瘤细胞的肿瘤发生和侵袭性。
Hum Mol Genet. 2015 May 1;24(9):2539-51. doi: 10.1093/hmg/ddv018. Epub 2015 Jan 23.
3
LINC00657 regulate colorectal carcinoma invasion and migration by enhancing heparanase expression through recruiting SMAD family member 2.LINC00657 通过招募 SMAD 家族成员 2 增强乙酰肝素酶表达来调控结直肠癌细胞侵袭和迁移。
Anticancer Drugs. 2022 Oct 1;33(9):803-814. doi: 10.1097/CAD.0000000000001323. Epub 2022 Aug 9.
4
Heparanase induces necroptosis of microvascular endothelial cells to promote the metastasis of hepatocellular carcinoma.乙酰肝素酶诱导微血管内皮细胞坏死性凋亡以促进肝细胞癌转移。
Cell Death Discov. 2021 Feb 17;7(1):33. doi: 10.1038/s41420-021-00411-5.
5
Heparanase Promotes Glioma Progression and Is Inversely Correlated with Patient Survival.乙酰肝素酶促进胶质瘤进展并与患者生存率呈负相关。
Mol Cancer Res. 2016 Dec;14(12):1243-1253. doi: 10.1158/1541-7786.MCR-16-0223. Epub 2016 Aug 26.
6
Curcumin inhibits CT26 cells metastasis by decreasing heparanase expression.姜黄素通过降低乙酰肝素酶表达抑制 CT26 细胞转移。
J Leukoc Biol. 2020 Dec;108(6):1727-1733. doi: 10.1002/JLB.1MA0620-357R. Epub 2020 Jul 8.
7
The acid-sensing ion channel, ASIC2, promotes invasion and metastasis of colorectal cancer under acidosis by activating the calcineurin/NFAT1 axis.酸感应离子通道 ASIC2 通过激活钙调神经磷酸酶/NFAT1 轴促进酸中毒下结直肠癌的侵袭和转移。
J Exp Clin Cancer Res. 2017 Sep 19;36(1):130. doi: 10.1186/s13046-017-0599-9.
8
Induction of heparanase via IL-10 correlates with a high infiltration of CD163+ M2-type tumor-associated macrophages in inflammatory breast carcinomas.通过白细胞介素-10诱导乙酰肝素酶与炎性乳腺癌中CD163 + M2型肿瘤相关巨噬细胞的高浸润相关。
Matrix Biol Plus. 2020 Feb 29;6-7:100030. doi: 10.1016/j.mbplus.2020.100030. eCollection 2020 May.
9
Heparanase is involved in proliferation and invasion of ovarian cancer cells.乙酰肝素酶参与卵巢癌细胞的增殖和侵袭。
Cancer Biomark. 2015;15(5):525-34. doi: 10.3233/CBM-150459.
10
Heparanase modulates the prognosis and development of BRAF V600E-mutant colorectal cancer by regulating AKT/p27Kip1/Cyclin E2 pathway.乙酰肝素酶通过调节AKT/p27Kip1/细胞周期蛋白E2通路来调控BRAF V600E突变型结直肠癌的预后和发展。
Oncogenesis. 2022 Sep 21;11(1):58. doi: 10.1038/s41389-022-00428-0.

引用本文的文献

1
Heparanase modulates the prognosis and development of BRAF V600E-mutant colorectal cancer by regulating AKT/p27Kip1/Cyclin E2 pathway.乙酰肝素酶通过调节AKT/p27Kip1/细胞周期蛋白E2通路来调控BRAF V600E突变型结直肠癌的预后和发展。
Oncogenesis. 2022 Sep 21;11(1):58. doi: 10.1038/s41389-022-00428-0.
2
Harnessing Human Papillomavirus' Natural Tropism to Target Tumors.利用人乳头瘤病毒的天然趋向性靶向肿瘤。
Viruses. 2022 Jul 28;14(8):1656. doi: 10.3390/v14081656.
3
Comprehensive bioinformatic analysis of MMP1 in hepatocellular carcinoma and establishment of relevant prognostic model.

本文引用的文献

1
Gemcitabine-induced heparanase promotes aggressiveness of pancreatic cancer cells via activating EGFR signaling.吉西他滨诱导的乙酰肝素酶通过激活表皮生长因子受体（EGFR）信号通路促进胰腺癌细胞的侵袭性。
Oncotarget. 2017 Apr 7;8(35):58417-58429. doi: 10.18632/oncotarget.16911. eCollection 2017 Aug 29.
2
Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future Directions.结直肠癌肝转移：不断演变的模式与未来方向
Cell Mol Gastroenterol Hepatol. 2017 Jan 20;3(2):163-173. doi: 10.1016/j.jcmgh.2017.01.006. eCollection 2017 Mar.
3
Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy.
全面的生物信息学分析 MMP1 在肝癌中的作用并建立相关预后模型。
Sci Rep. 2022 Aug 10;12(1):13639. doi: 10.1038/s41598-022-17954-x.
4
CREB3 Plays an Important Role in HPSE-Facilitated HSV-1 Release in Human Corneal Epithelial Cells.CREB3 在 HPSE 促进 HSV-1 从人角膜上皮细胞释放中发挥重要作用。
Viruses. 2022 May 28;14(6):1171. doi: 10.3390/v14061171.
5
The transcription factor Rreb1 regulates epithelial architecture, invasiveness, and vasculogenesis in early mouse embryos.转录因子 Rreb1 调节早期小鼠胚胎中的上皮结构、侵袭和血管生成。
Elife. 2021 Apr 30;10:e64811. doi: 10.7554/eLife.64811.
6
Heparanase induces necroptosis of microvascular endothelial cells to promote the metastasis of hepatocellular carcinoma.乙酰肝素酶诱导微血管内皮细胞坏死性凋亡以促进肝细胞癌转移。
Cell Death Discov. 2021 Feb 17;7(1):33. doi: 10.1038/s41420-021-00411-5.
7
Prophylactical Low Dose Whole-Liver Irradiation Inhibited Colorectal Liver Metastasis by Regulating Hepatic Niche in Mice.预防性低剂量全肝照射通过调节小鼠肝脏微环境抑制结直肠癌肝转移。
Onco Targets Ther. 2020 Aug 24;13:8451-8462. doi: 10.2147/OTT.S263858. eCollection 2020.
8
[Heparanase promotes trans-endothelial migration of hepatocarcinoma cells by inducing apoptosis of microvascular endothelial cells].[乙酰肝素酶通过诱导微血管内皮细胞凋亡促进肝癌细胞的跨内皮迁移]
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Aug 30;40(8):1065-1071. doi: 10.12122/j.issn.1673-4254.2020.08.01.
9
Heparanase potentiates the invasion and migration of pancreatic cancer cells via epithelial‑to‑mesenchymal transition through the Wnt/β‑catenin pathway.乙酰肝素酶通过 Wnt/β-连环蛋白通路通过上皮-间充质转化增强胰腺癌细胞的侵袭和迁移。
Oncol Rep. 2020 Aug;44(2):711-721. doi: 10.3892/or.2020.7641. Epub 2020 Jun 10.
乙酰肝素酶对癌症、自噬和炎症的调控：治疗的新机制与靶点
FEBS J. 2017 Jan;284(1):42-55. doi: 10.1111/febs.13932. Epub 2016 Nov 16.
4
Heparanase Promotes Glioma Progression and Is Inversely Correlated with Patient Survival.乙酰肝素酶促进胶质瘤进展并与患者生存率呈负相关。
Mol Cancer Res. 2016 Dec;14(12):1243-1253. doi: 10.1158/1541-7786.MCR-16-0223. Epub 2016 Aug 26.
5
Global patterns and trends in colorectal cancer incidence and mortality.全球结直肠癌发病率和死亡率的模式和趋势。
Gut. 2017 Apr;66(4):683-691. doi: 10.1136/gutjnl-2015-310912. Epub 2016 Jan 27.
6
Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis.乙酰肝素酶中和抗体可减弱淋巴瘤肿瘤的生长和转移。
Proc Natl Acad Sci U S A. 2016 Jan 19;113(3):704-9. doi: 10.1073/pnas.1519453113. Epub 2016 Jan 4.
7
Nicotine enhances invasion and metastasis of human colorectal cancer cells through the nicotinic acetylcholine receptor downstream p38 MAPK signaling pathway.尼古丁通过烟碱型乙酰胆碱受体下游的p38丝裂原活化蛋白激酶信号通路增强人结肠癌细胞的侵袭和转移。
Oncol Rep. 2016 Jan;35(1):205-10. doi: 10.3892/or.2015.4363. Epub 2015 Oct 30.
8
Heparanase is involved in proliferation and invasion of ovarian cancer cells.乙酰肝素酶参与卵巢癌细胞的增殖和侵袭。
Cancer Biomark. 2015;15(5):525-34. doi: 10.3233/CBM-150459.
9
The Role of Heparanase and Sulfatases in the Modification of Heparan Sulfate Proteoglycans within the Tumor Microenvironment and Opportunities for Novel Cancer Therapeutics.肝素酶和硫酸酯酶在肿瘤微环境中修饰硫酸乙酰肝素蛋白聚糖中的作用及新型癌症治疗的机会。
Front Oncol. 2014 Jul 24;4:195. doi: 10.3389/fonc.2014.00195. eCollection 2014.
10
Development and applications of CRISPR-Cas9 for genome engineering.用于基因组工程的CRISPR-Cas9技术的开发与应用。
Cell. 2014 Jun 5;157(6):1262-1278. doi: 10.1016/j.cell.2014.05.010.