• 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

STIM1 和 Orai1 表达增强对 Huh-7 肝癌起始细胞功能的影响。

Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells.

机构信息

Izmir Biomedicine and Genome Center (IBG), Dokuz Eylul University, 35340, Izmir, Turkey.

Department of Pharmacology, Faculty of Pharmacy, Ege University, 35100, Izmir, Turkey.

出版信息

BMC Cancer. 2019 Jul 31;19(1):751. doi: 10.1186/s12885-019-5947-z.

DOI:10.1186/s12885-019-5947-z
PMID:31366337
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6668110/
Abstract

BACKGROUND

The endoplasmic reticulum (ER) Ca sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated with poor patient prognosis. Therefore, this study investigated the functional consequences of enhanced expression of STIM1 and Orai1 in a tumor-initiating subpopulation of Huh-7 hepatocellular carcinoma (HCC) cells that express epithelial cell adhesion molecule (EpCAM) and Prominin 1 (CD133).

METHODS

We performed qRT-PCR, intracellular Ca monitoring, protein analyses, and real-time cell proliferation assays on EpCAM(+)CD133(+) subpopulation of tumor-initiating Huh-7 HCC cells expressing high levels of STIM1 and/or Orai1. Statistical significance between the means of two groups was evaluated using unpaired Student's t-test.

RESULTS

Enhanced STIM1 expression significantly increased ER Ca release and proliferation rate of EpCAM(+)CD133(+) cells.

CONCLUSION

STIM1 overexpression may facilitate cancer cell survival by increasing ER Ca-buffering capacity, which makes more Ca available for the cytosolic events, on the other hand, possibly preventing Ca-dependent enzymatic activity in mitochondria whose Ca uniporter requires much higher cytosolic Ca levels.

摘要

背景

内质网（ER）钙传感器基质相互作用分子 1（STIM1）激活质膜（PM）通道 Orai1，以介导 ER 储存耗竭时的储存操纵钙内流（SOCE）。在癌组织中 STIM1 的高表达与患者预后不良有关。因此，本研究研究了在表达上皮细胞黏附分子（EpCAM）和 Prominin 1（CD133）的 Huh-7 肝癌（HCC）起始肿瘤亚群中增强表达 STIM1 和 Orai1 的功能后果。

方法

我们对高表达 STIM1 和/或 Orai1 的 Huh-7 HCC 起始肿瘤细胞的 EpCAM(+)CD133(+)亚群进行 qRT-PCR、细胞内 Ca 监测、蛋白分析和实时细胞增殖测定。两组均值间的统计学差异采用未配对 Student's t 检验进行评估。

结果

增强的 STIM1 表达显著增加了 EpCAM(+)CD133(+)细胞的 ER Ca 释放和增殖率。

结论

STIM1 的过表达可能通过增加 ER Ca 缓冲能力来促进癌细胞的存活，从而使更多的 Ca 可用于细胞溶质事件，另一方面，可能防止依赖 Ca 的线粒体酶活性，其 Ca 单向转运蛋白需要更高的细胞溶质 Ca 水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/61173e1935a3/12885_2019_5947_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/ee2f23fe34ed/12885_2019_5947_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/96ce2f68821f/12885_2019_5947_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/e044ef18e1f7/12885_2019_5947_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/98bdfe50145c/12885_2019_5947_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/c388136a7c5d/12885_2019_5947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/fd45dbcfd6bb/12885_2019_5947_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/dfbc89dec996/12885_2019_5947_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/e87daa3332fb/12885_2019_5947_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/709cb3526bbb/12885_2019_5947_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/96f851c99720/12885_2019_5947_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/ec2377b421eb/12885_2019_5947_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/6e0fc60234c1/12885_2019_5947_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/61173e1935a3/12885_2019_5947_Fig13_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/ee2f23fe34ed/12885_2019_5947_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/96ce2f68821f/12885_2019_5947_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/e044ef18e1f7/12885_2019_5947_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/98bdfe50145c/12885_2019_5947_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/c388136a7c5d/12885_2019_5947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/fd45dbcfd6bb/12885_2019_5947_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/dfbc89dec996/12885_2019_5947_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/e87daa3332fb/12885_2019_5947_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/709cb3526bbb/12885_2019_5947_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/96f851c99720/12885_2019_5947_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/ec2377b421eb/12885_2019_5947_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/6e0fc60234c1/12885_2019_5947_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da50/6668110/61173e1935a3/12885_2019_5947_Fig13_HTML.jpg

相似文献

1
Functional consequences of enhanced expression of STIM1 and Orai1 in Huh-7 hepatocellular carcinoma tumor-initiating cells.STIM1 和 Orai1 表达增强对 Huh-7 肝癌起始细胞功能的影响。
BMC Cancer. 2019 Jul 31;19(1):751. doi: 10.1186/s12885-019-5947-z.
2
The store-operated Ca entry complex comprises a small cluster of STIM1 associated with one Orai1 channel.钙库操纵性钙内流通道复合物由一小簇与一个 Orai1 通道相关联的 STIM1 组成。
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10). doi: 10.1073/pnas.2010789118.
3
The distinct role of STIM1 and STIM2 in the regulation of store-operated Ca entry and cellular function.STIM1 和 STIM2 在调节钙库操纵性钙内流和细胞功能中的独特作用。
J Cell Physiol. 2019 Jun;234(6):8727-8739. doi: 10.1002/jcp.27532. Epub 2018 Oct 14.
4
Upregulation of Orai1 and STIM1 expression as well as store-operated Ca entry in ovary carcinoma cells by placental growth factor.胎盘生长因子上调卵巢癌细胞中 Orai1 和 STIM1 的表达及钙库操纵性钙内流。
Biochem Biophys Res Commun. 2019 May 7;512(3):467-472. doi: 10.1016/j.bbrc.2019.03.025. Epub 2019 Mar 20.
5
Filamin A Modulates Store-Operated Ca Entry by Regulating STIM1 (Stromal Interaction Molecule 1)-Orai1 Association in Human Platelets.细丝蛋白 A 通过调节血小板中 STIM1（基质相互作用分子 1）-Orai1 复合物的形成来调节 Store 操作型钙内流。
Arterioscler Thromb Vasc Biol. 2018 Feb;38(2):386-397. doi: 10.1161/ATVBAHA.117.310139. Epub 2017 Dec 28.
6
Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer.Orai1 和 STIM1 表达水平升高会上调 MACC1 的表达，从而促进人胃癌肿瘤细胞的增殖、代谢、迁移和侵袭。
Cancer Lett. 2016 Oct 10;381(1):31-40. doi: 10.1016/j.canlet.2016.07.014. Epub 2016 Jul 16.
7
STIM1 Phosphorylation at Y361 Recruits Orai1 to STIM1 Puncta and Induces Ca Entry.STIM1 上 Y361 的磷酸化募集 Orai1 到 STIM1 斑点并诱导 Ca 内流。
Sci Rep. 2017 Feb 20;7:42758. doi: 10.1038/srep42758.
8
STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM Junctions.STIM2 诱导 STIM1 激活构象以控制 ER-PM 连接中的 Orai1 功能。
Cell Rep. 2018 Apr 10;23(2):522-534. doi: 10.1016/j.celrep.2018.03.065.
9
Interplay between ER Ca Binding Proteins, STIM1 and STIM2, Is Required for Store-Operated Ca Entry.内质网 Ca2+ 结合蛋白、STIM1 和 STIM2 之间的相互作用是钙库操纵性钙内流所必需的。
Int J Mol Sci. 2018 May 19;19(5):1522. doi: 10.3390/ijms19051522.
10
Phosphate-induced ORAI1 expression and store-operated Ca entry in aortic smooth muscle cells.磷酸盐诱导的 ORAI1 表达和储存操纵的钙内流在主动脉平滑肌细胞中。
J Mol Med (Berl). 2019 Oct;97(10):1465-1475. doi: 10.1007/s00109-019-01824-7. Epub 2019 Aug 5.

引用本文的文献

1
Calcium Homeostasis Disrupted-How Store-Operated Calcium Entry Factor SARAF Silencing Impacts HepG2 Liver Cancer Cells.钙稳态失衡——储存式钙内流因子SARAF沉默对肝癌HepG2细胞的影响
Int J Mol Sci. 2025 May 7;26(9):4426. doi: 10.3390/ijms26094426.
2
The Cytoplasmic Region of SARAF Reduces Triple-Negative Breast Cancer Metastasis through the Regulation of Store-Operated Calcium Entry.SARAF 的细胞质区域通过调节钙库操纵性钙内流减少三阴性乳腺癌转移。
Int J Mol Sci. 2023 Mar 10;24(6):5306. doi: 10.3390/ijms24065306.
3
Blockade of store-operated calcium entry sensitizes breast cancer cells to cisplatin therapy via modulating inflammatory response.

本文引用的文献

1
STIM1 overexpression in hypoxia microenvironment contributes to pancreatic carcinoma progression.缺氧微环境中STIM1的过表达促进胰腺癌进展。
Cancer Biol Med. 2019 Feb;16(1):100-108. doi: 10.20892/j.issn.2095-3941.2018.0304.
2
Numbers count: How STIM and Orai stoichiometry affect store-operated calcium entry.数字说话：STIM 和 Orai 计量如何影响钙库操纵性钙内流。
Cell Calcium. 2019 May;79:35-43. doi: 10.1016/j.ceca.2019.02.002. Epub 2019 Feb 12.
3
Ion Channels in Cancer: Are Cancer Hallmarks Oncochannelopathies?离子通道与癌症：癌症特征性病变是离子通道病吗？
阻断钙库操纵性钙内流通过调节炎症反应使乳腺癌细胞对顺铂治疗敏感。
Saudi Pharm J. 2023 Feb;31(2):245-254. doi: 10.1016/j.jsps.2022.12.009. Epub 2022 Dec 24.
4
Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line.乙肝病毒驱动的基因表达调控对Huh-7肝癌细胞系干细胞样亚群的潜在影响
J Pers Med. 2022 Dec 14;12(12):2065. doi: 10.3390/jpm12122065.
5
Ca Transportome and the Interorganelle Communication in Hepatocellular Carcinoma.钙转运体组和肝细胞癌中的细胞器间通讯。
Cells. 2022 Feb 26;11(5):815. doi: 10.3390/cells11050815.
6
PKC-β modulates Ca mobilization through Stim1 phosphorylation.PKC-β 通过磷酸化 Stim1 调节 Ca2+ 动员。
Genes Genomics. 2022 May;44(5):571-582. doi: 10.1007/s13258-022-01230-3. Epub 2022 Mar 7.
7
STIM1 Controls the Focal Adhesion Dynamics and Cell Migration by Regulating SOCE in Osteosarcoma.STIM1 通过调控骨肉瘤中的 SOCE 控制黏着斑动态和细胞迁移。
Int J Mol Sci. 2021 Dec 23;23(1):162. doi: 10.3390/ijms23010162.
8
Role of Calcium Homeostasis in Modulating EMT in Cancer.钙稳态在调节癌症上皮-间质转化中的作用。
Biomedicines. 2021 Sep 11;9(9):1200. doi: 10.3390/biomedicines9091200.
9
Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.细胞内钙信号传导的进展揭示了癌症治疗中尚未开发的靶点。
Biomedicines. 2021 Aug 24;9(9):1077. doi: 10.3390/biomedicines9091077.
10
Stromal interaction molecule 1 (STIM1) knock down attenuates invasion and proliferation and enhances the expression of thyroid-specific proteins in human follicular thyroid cancer cells.基质相互作用分子 1（STIM1）敲低可抑制人甲状腺滤泡癌细胞的侵袭和增殖，并增强甲状腺特异性蛋白的表达。
Cell Mol Life Sci. 2021 Aug;78(15):5827-5846. doi: 10.1007/s00018-021-03880-0. Epub 2021 Jun 21.
Physiol Rev. 2018 Apr 1;98(2):559-621. doi: 10.1152/physrev.00044.2016.
4
Expression of STIM1 is associated with tumor aggressiveness and poor prognosis in breast cancer.STIM1的表达与乳腺癌的肿瘤侵袭性及不良预后相关。
Pathol Res Pract. 2017 Sep;213(9):1043-1047. doi: 10.1016/j.prp.2017.08.006. Epub 2017 Aug 25.
5
Cancer stem cell surface markers on normal stem cells.正常干细胞上的癌症干细胞表面标志物。
BMB Rep. 2017 Jun;50(6):285-298. doi: 10.5483/bmbrep.2017.50.6.039.
6
Inhibition of Orai1-mediated Ca entry enhances chemosensitivity of HepG2 hepatocarcinoma cells to 5-fluorouracil.抑制Orai1介导的钙离子内流可增强肝癌细胞HepG2对5-氟尿嘧啶的化疗敏感性。
J Cell Mol Med. 2017 May;21(5):904-915. doi: 10.1111/jcmm.13029. Epub 2016 Nov 23.
7
Elevated Orai1 and STIM1 expressions upregulate MACC1 expression to promote tumor cell proliferation, metabolism, migration, and invasion in human gastric cancer.Orai1 和 STIM1 表达水平升高会上调 MACC1 的表达，从而促进人胃癌肿瘤细胞的增殖、代谢、迁移和侵袭。
Cancer Lett. 2016 Oct 10;381(1):31-40. doi: 10.1016/j.canlet.2016.07.014. Epub 2016 Jul 16.
8
Cancer Stem Cell Quiescence and Plasticity as Major Challenges in Cancer Therapy.癌症干细胞的静止与可塑性：癌症治疗中的主要挑战
Stem Cells Int. 2016;2016:1740936. doi: 10.1155/2016/1740936. Epub 2016 Jun 21.
9
To wake up cancer stem cells, or to let them sleep, that is the question.唤醒癌症干细胞，还是让它们沉睡，这是个问题。
Cancer Sci. 2016 Jul;107(7):875-81. doi: 10.1111/cas.12958. Epub 2016 Jun 20.
10
Liver cancer stem cell markers: Progression and therapeutic implications.肝癌干细胞标志物：进展与治疗意义
World J Gastroenterol. 2016 Apr 7;22(13):3547-57. doi: 10.3748/wjg.v22.i13.3547.