• 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

ZEB1 和 IL-6/11-STAT3 信号协同作用，通过差异调节 S100 蛋白的表达来定义胰腺癌细胞的侵袭潜力。

ZEB1 and IL-6/11-STAT3 signalling cooperate to define invasive potential of pancreatic cancer cells via differential regulation of the expression of S100 proteins.

机构信息

Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

College of Medicine, University of Duhokl, Kurdistan region, Duhok, Iraq.

出版信息

Br J Cancer. 2019 Jul;121(1):65-75. doi: 10.1038/s41416-019-0483-9. Epub 2019 May 24.

DOI:10.1038/s41416-019-0483-9
PMID:31123345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6738112/
Abstract

BACKGROUND

S100 proteins have been implicated in various aspects of cancer, including epithelial-mesenchymal transitions (EMT), invasion and metastasis, and also in inflammatory disorders. Here we examined the impact of individual members of this family on the invasion of pancreatic ductal adenocarcinoma (PDAC) cells, and their regulation by EMT and inflammation.

METHODS

Invasion of PDAC cells was analysed in zebrafish embryo xenografts and in transwell invasion assays. Expression and regulation of S100 proteins was studied in vitro by immunoblotting, quantitative PCR and immunofluorescence, and in pancreatic lesions by immunohistochemistry.

RESULTS

Whereas the expression of most S100 proteins is characteristic for epithelial PDAC cell lines, S100A4 and S100A6 are strongly expressed in mesenchymal cells and upregulated by ZEB1. S100A4/A6 and epithelial protein S100A14 respectively promote and represses cell invasion. IL-6/11-STAT3 pathway stimulates expression of most S100 proteins. ZEB1 synergises with IL-6/11-STAT3 to upregulate S100A4/A6, but nullifies the effect of inflammation on S100A14 expression.

CONCLUSION

EMT/ZEB1 and IL-6/11-STAT3 signalling act independently and congregate to establish the expression pattern of S100 proteins, which drives invasion. Although ZEB1 regulates expression of S100 family members, these effects are masked by IL-6/11-STAT3 signalling, and S100 proteins cannot be considered as bona fide EMT markers in PDAC.

摘要

背景

S100 蛋白参与了癌症的多个方面，包括上皮-间充质转化（EMT）、侵袭和转移，以及炎症性疾病。在这里，我们研究了这个家族的各个成员对胰腺导管腺癌（PDAC）细胞侵袭的影响，以及 EMT 和炎症对其的调节。

方法

通过斑马鱼胚胎异种移植和 Transwell 侵袭实验分析 PDAC 细胞的侵袭。通过免疫印迹、定量 PCR 和免疫荧光在体外研究 S100 蛋白的表达和调节，通过免疫组化在胰腺病变中研究。

结果

虽然大多数 S100 蛋白的表达特征是上皮性 PDAC 细胞系，但 S100A4 和 S100A6 在间充质细胞中强烈表达，并被 ZEB1 上调。S100A4/A6 和上皮蛋白 S100A14 分别促进和抑制细胞侵袭。IL-6/11-STAT3 通路刺激大多数 S100 蛋白的表达。ZEB1 与 IL-6/11-STAT3 协同作用上调 S100A4/A6，但使炎症对 S100A14 表达的影响无效。

结论

EMT/ZEB1 和 IL-6/11-STAT3 信号独立作用并聚集起来建立 S100 蛋白的表达模式，从而驱动侵袭。尽管 ZEB1 调节 S100 家族成员的表达，但这些影响被 IL-6/11-STAT3 信号掩盖，并且 S100 蛋白不能被视为 PDAC 中真正的 EMT 标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/3f308f409aa5/41416_2019_483_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/91fa7557ad94/41416_2019_483_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/e55a4ff3e3bb/41416_2019_483_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/f9e4782495bb/41416_2019_483_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/ab0354a5c4f4/41416_2019_483_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/9e3d77919f4c/41416_2019_483_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/3f308f409aa5/41416_2019_483_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/91fa7557ad94/41416_2019_483_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/e55a4ff3e3bb/41416_2019_483_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/f9e4782495bb/41416_2019_483_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/ab0354a5c4f4/41416_2019_483_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/9e3d77919f4c/41416_2019_483_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c90/6738112/3f308f409aa5/41416_2019_483_Fig6_HTML.jpg

相似文献

1
ZEB1 and IL-6/11-STAT3 signalling cooperate to define invasive potential of pancreatic cancer cells via differential regulation of the expression of S100 proteins.ZEB1 和 IL-6/11-STAT3 信号协同作用，通过差异调节 S100 蛋白的表达来定义胰腺癌细胞的侵袭潜力。
Br J Cancer. 2019 Jul;121(1):65-75. doi: 10.1038/s41416-019-0483-9. Epub 2019 May 24.
2
Paracrine IL-6 signaling mediates the effects of pancreatic stellate cells on epithelial-mesenchymal transition via Stat3/Nrf2 pathway in pancreatic cancer cells.旁分泌 IL-6 信号通过 Stat3/Nrf2 通路介导胰腺星状细胞对胰腺癌细胞上皮间质转化的影响。
Biochim Biophys Acta Gen Subj. 2017 Feb;1861(2):296-306. doi: 10.1016/j.bbagen.2016.10.006. Epub 2016 Oct 14.
3
Sonic hedgehog-Gli1 signaling pathway regulates the epithelial mesenchymal transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells.音猬因子-Gli1信号通路通过介导胰腺癌细胞中的一个新靶基因S100A4来调节上皮-间质转化（EMT）。
PLoS One. 2014 Jul 29;9(7):e96441. doi: 10.1371/journal.pone.0096441. eCollection 2014.
4
S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through β-catenin in pancreatic cancer cell line.S100钙结合蛋白A6通过β-连环蛋白促进胰腺癌细胞系的上皮-间质转化。
PLoS One. 2015 Mar 23;10(3):e0121319. doi: 10.1371/journal.pone.0121319. eCollection 2015.
5
UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC.UBE2C 被 miR-548e-5p 直接靶向，增加了与非小细胞肺癌中 EMT 标志物蛋白锌指 E-box 结合同源框 1/2 相互作用的癌细胞的细胞生长和侵袭能力。
Theranostics. 2019 Mar 17;9(7):2036-2055. doi: 10.7150/thno.32738. eCollection 2019.
6
The effects and mechanisms of blockage of STAT3 signaling pathway on IL-6 inducing EMT in human pancreatic cancer cells in vitro.阻断 STAT3 信号通路对体外人胰腺癌细胞中 IL-6 诱导 EMT 的作用及其机制。
Neoplasma. 2011;58(5):396-405. doi: 10.4149/neo_2011_05_396.
7
LncRNA ADPGK-AS1 promotes pancreatic cancer progression through activating ZEB1-mediated epithelial-mesenchymal transition.长链非编码 RNA ADPGK-AS1 通过激活 ZEB1 介导的上皮-间充质转化促进胰腺癌进展。
Cancer Biol Ther. 2018 Jul 3;19(7):573-583. doi: 10.1080/15384047.2018.1423912. Epub 2018 Apr 19.
8
Src promotes EGF-induced epithelial-to-mesenchymal transition and migration in gastric cancer cells by upregulating ZEB1 and ZEB2 through AKT.Src 通过激活 AKT 上调 ZEB1 和 ZEB2 促进表皮生长因子诱导的胃癌细胞上皮间质转化和迁移。
Cell Biol Int. 2018 Mar;42(3):294-302. doi: 10.1002/cbin.10894. Epub 2017 Nov 15.
9
MiR-652 inhibits acidic microenvironment-induced epithelial-mesenchymal transition of pancreatic cancer cells by targeting ZEB1.微小RNA-652通过靶向锌指E盒结合蛋白1抑制酸性微环境诱导的胰腺癌细胞上皮-间质转化。
Oncotarget. 2015 Nov 24;6(37):39661-75. doi: 10.18632/oncotarget.5350.
10
Vasohibin 2 promotes malignant behaviors of pancreatic cancer cells by inducing epithelial-mesenchymal transition via Hedgehog signaling pathway.血管抑素 2 通过 Hedgehog 信号通路诱导上皮-间充质转化促进胰腺癌恶性行为。
Cancer Med. 2018 Nov;7(11):5567-5576. doi: 10.1002/cam4.1752. Epub 2018 Oct 14.

引用本文的文献

1
ZEB1 expression in Th17 cells correlated with p-STAT3 in human apical periodontitis.人根尖周炎中，Th17细胞中的ZEB1表达与磷酸化信号转导及转录激活因子3（p-STAT3）相关。
BMC Oral Health. 2025 Feb 27;25(1):315. doi: 10.1186/s12903-025-05633-y.
2
Elevated Serum IL-6 as a Negative Prognostic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Validation.血清白细胞介素-6升高作为胶质母细胞瘤的负性预后生物标志物：整合生物信息学与临床验证
J Cancer. 2025 Jan 1;16(3):802-811. doi: 10.7150/jca.104759. eCollection 2025.
3
A human STAT3 gain-of-function variant drives local Th17 dysregulation and skin inflammation in mice.

本文引用的文献

1
S100A4 in cancer progression and metastasis: A systematic review.S100A4在癌症进展和转移中的作用：一项系统综述。
Oncotarget. 2017 May 19;8(42):73219-73239. doi: 10.18632/oncotarget.18016. eCollection 2017 Sep 22.
2
Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence.1q21.3 染色体扩增是乳腺癌复发的一种可追踪的生物标志物和可操作的靶点。
Nat Med. 2017 Nov;23(11):1319-1330. doi: 10.1038/nm.4405. Epub 2017 Sep 25.
3
S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma.
人类 STAT3 功能获得性变异可导致小鼠局部 Th17 失调和皮肤炎症。
J Exp Med. 2024 Aug 5;221(8). doi: 10.1084/jem.20232091. Epub 2024 Jun 11.
4
Stat3 activation-triggered transcriptional networks govern the early stage of HBV-induced hepatic inflammation.Stat3 激活触发的转录网络调控 HBV 诱导的肝炎症的早期阶段。
mBio. 2024 Apr 10;15(4):e0306823. doi: 10.1128/mbio.03068-23. Epub 2024 Mar 5.
5
Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity.通过上皮-间充质转化实现致癌 RAS 的协同促肿瘤发生适应性。
Sci Adv. 2024 Feb 16;10(7):eadi1736. doi: 10.1126/sciadv.adi1736. Epub 2024 Feb 14.
6
An integrated overview of the immunosuppression features in the tumor microenvironment of pancreatic cancer.胰腺癌肿瘤微环境中免疫抑制特征的综合概述。
Front Immunol. 2023 Sep 12;14:1258538. doi: 10.3389/fimmu.2023.1258538. eCollection 2023.
7
S100s and HMGB1 Crosstalk in Pancreatic Cancer Tumors.S100s 与 HMGB1 在胰腺癌肿瘤中的相互作用。
Biomolecules. 2023 Jul 28;13(8):1175. doi: 10.3390/biom13081175.
8
An oncolytic adenovirus coding for a variant interleukin 2 cytokine improves response to chemotherapy through enhancement of effector lymphocyte cytotoxicity, fibroblast compartment modulation and mitotic slippage.一种编码变异白细胞介素 2 细胞因子的溶瘤腺病毒通过增强效应淋巴细胞的细胞毒性、成纤维细胞区室调节和有丝分裂滑动，改善了对化疗的反应。
Front Immunol. 2023 Jul 5;14:1171083. doi: 10.3389/fimmu.2023.1171083. eCollection 2023.
9
Molecular profile of metastasis, cell plasticity and EMT in pancreatic cancer: a pre-clinical connection to aggressiveness and drug resistance.胰腺癌转移、细胞可塑性和 EMT 的分子特征：临床前侵袭性和耐药性的联系。
Cancer Metastasis Rev. 2024 Mar;43(1):29-53. doi: 10.1007/s10555-023-10125-y. Epub 2023 Jul 15.
10
Src-FAK Signaling Mediates Interleukin 6-Induced HCT116 Colorectal Cancer Epithelial-Mesenchymal Transition.Src-FAK 信号转导介导白细胞介素 6 诱导的 HCT116 结直肠癌细胞上皮-间充质转化。
Int J Mol Sci. 2023 Apr 2;24(7):6650. doi: 10.3390/ijms24076650.
S100A4是一种胶质瘤干细胞的生物标志物和调节因子，对胶质母细胞瘤的间充质转化至关重要。
Cancer Res. 2017 Oct 1;77(19):5360-5373. doi: 10.1158/0008-5472.CAN-17-1294. Epub 2017 Aug 14.
4
Short stretches of rare codons regulate translation of the transcription factor ZEB2 in cancer cells.短片段稀有密码子调控癌细胞中转录因子ZEB2的翻译。
Oncogene. 2017 Nov 23;36(47):6640-6648. doi: 10.1038/onc.2017.273. Epub 2017 Aug 7.
5
S100A6 protein: functional roles.S100A6蛋白：功能作用
Cell Mol Life Sci. 2017 Aug;74(15):2749-2760. doi: 10.1007/s00018-017-2526-9. Epub 2017 Apr 17.
6
The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer.EMT 激活物 Zeb1 是细胞可塑性的关键因素，并促进胰腺癌转移。
Nat Cell Biol. 2017 May;19(5):518-529. doi: 10.1038/ncb3513. Epub 2017 Apr 17.
7
Pancreatic stellate cell secreted IL-6 stimulates STAT3 dependent invasiveness of pancreatic intraepithelial neoplasia and cancer cells.胰腺星状细胞分泌的白细胞介素-6刺激胰腺上皮内瘤变和癌细胞的STAT3依赖性侵袭。
Oncotarget. 2016 Oct 4;7(40):65982-65992. doi: 10.18632/oncotarget.11786.
8
EMT: 2016.EMT：2016 年。
Cell. 2016 Jun 30;166(1):21-45. doi: 10.1016/j.cell.2016.06.028.
9
Genetics and biology of pancreatic ductal adenocarcinoma.胰腺导管腺癌的遗传学与生物学
Genes Dev. 2016 Feb 15;30(4):355-85. doi: 10.1101/gad.275776.115.
10
STAT3 selectively interacts with Smad3 to antagonize TGF-β signalling.信号转导及转录激活因子3（STAT3）与Smad3特异性相互作用，以拮抗转化生长因子-β（TGF-β）信号传导。
Oncogene. 2016 Aug 18;35(33):4388-98. doi: 10.1038/onc.2015.446. Epub 2015 Nov 30.