PI3K/Akt活性对人癌细胞系中HIF靶基因CA9和VEGF的表达具有不同的细胞特异性作用。
PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines.
作者信息
Shafee Norazizah, Kaluz Stefan, Ru Ning, Stanbridge Eric J
机构信息
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
出版信息
Cancer Lett. 2009 Sep 8;282(1):109-15. doi: 10.1016/j.canlet.2009.03.004. Epub 2009 Apr 1.
Abstract
The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1alpha and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N-ras allele), correlated with increased PI3K activity. Constitutive activation of the PI3K pathway in MCH603/PI3K(act) cells increased HIF-1alpha but, surprisingly, decreased CAIX levels. The cell-type specific inhibitory effect on CAIX was confirmed at the transcriptional level whereas epigenetic modifications of CA9 were ruled out. In summary, our data do not substantiate the generalization that PI3K upregulation leads to increased HIF activity.
摘要
磷脂酰肌醇3激酶/蛋白激酶B（PI3K）信号通路调节缺氧诱导因子（HIF）的活性。与衍生的MCH603细胞（缺失突变型N-ras等位基因）相比，HT10806TG纤维肉瘤细胞（突变型N-ras等位基因）中HIF-1α和碳酸酐酶IX（CAIX，一种缺氧诱导基因）的高表达与PI3K活性增加相关。MCH603/PI3K(act)细胞中PI3K信号通路的组成性激活增加了HIF-1α，但令人惊讶的是，降低了CAIX水平。在转录水平证实了对CAIX的细胞类型特异性抑制作用，而排除了CA9的表观遗传修饰。总之，我们的数据并不支持PI3K上调导致HIF活性增加这一普遍观点。
相似文献
1
PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines.PI3K/Akt活性对人癌细胞系中HIF靶基因CA9和VEGF的表达具有不同的细胞特异性作用。
Cancer Lett. 2009 Sep 8;282(1):109-15. doi: 10.1016/j.canlet.2009.03.004. Epub 2009 Apr 1.
2
3
Expression patterns of the hypoxia-related genes osteopontin, CA9, erythropoietin, VEGF and HIF-1alpha in human glioma in vitro and in vivo.缺氧相关基因骨桥蛋白、碳酸酐酶9、促红细胞生成素、血管内皮生长因子和缺氧诱导因子-1α在人胶质瘤体内外的表达模式
Radiother Oncol. 2007 Jun;83(3):398-405. doi: 10.1016/j.radonc.2007.05.003. Epub 2007 May 23.
4
Increased activation of the hypoxia-inducible factor pathway in varicose veins.静脉曲胀中缺氧诱导因子通路的激活增加。
J Vasc Surg. 2012 May;55(5):1427-39. doi: 10.1016/j.jvs.2011.10.111. Epub 2012 Jan 24.
5
Src induces expression of carbonic anhydrase IX via hypoxia-inducible factor 1.Src 通过缺氧诱导因子 1 诱导碳酸酐酶 IX 的表达。
Oncol Rep. 2010 Mar;23(3):869-74.
6
Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show?肿瘤及缺氧标志物碳酸酐酶9的转录调控：单一转录因子（缺氧诱导因子-1）的作用？
Biochim Biophys Acta. 2009 Apr;1795(2):162-72. doi: 10.1016/j.bbcan.2009.01.001. Epub 2009 Jan 22.
7
DNA damage is a prerequisite for p53-mediated proteasomal degradation of HIF-1alpha in hypoxic cells and downregulation of the hypoxia marker carbonic anhydrase IX.DNA损伤是低氧细胞中p53介导的HIF-1α蛋白酶体降解及低氧标志物碳酸酐酶IX下调的前提条件。
Mol Cell Biol. 2004 Jul;24(13):5757-66. doi: 10.1128/MCB.24.13.5757-5766.2004.
8
9
MAPK pathway contributes to density- and hypoxia-induced expression of the tumor-associated carbonic anhydrase IX.丝裂原活化蛋白激酶（MAPK）信号通路有助于肿瘤相关碳酸酐酶IX在密度和缺氧诱导下的表达。
Biochim Biophys Acta. 2005 May 25;1729(1):41-9. doi: 10.1016/j.bbaexp.2005.03.003. Epub 2005 Mar 23.
10
Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway.ras和冯·希佩尔-林道（VHL）基因突变对缺氧诱导因子（HIF）-1α、HIF-2α及血管内皮生长因子表达的影响及其受磷脂酰肌醇3'-激酶/蛋白激酶B信号通路的调控
Cancer Res. 2001 Oct 1;61(19):7349-55.
引用本文的文献
1
Metabolic Reprogramming in Thyroid Cancer.甲状腺癌中的代谢重编程。
Endocrinol Metab (Seoul). 2024 Jun;39(3):425-444. doi: 10.3803/EnM.2023.1802. Epub 2024 Jun 10.
2
Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop.间质干细胞作为胶质瘤外泌体免疫抑制信号的倍增器，通过 miR-21/SP1/DNMT1 正反馈环增强 MDSC 的免疫抑制活性。
J Nanobiotechnology. 2023 Jul 22;21(1):233. doi: 10.1186/s12951-023-01997-x.
3
Hypoxia-regulated carbonic anhydrase IX (CAIX) protein is an independent prognostic indicator in triple negative breast cancer.缺氧调节碳酸酐酶 IX（CAIX）蛋白是三阴性乳腺癌的独立预后指标。
Breast Cancer Res. 2022 Jun 3;24(1):38. doi: 10.1186/s13058-022-01532-0.
4
Carbonic anhydrase IX and hypoxia-inducible factor 1 attenuate cardiac dysfunction after myocardial infarction.碳酸酐酶 IX 和缺氧诱导因子 1 可减轻心肌梗死后的心脏功能障碍。
Pflugers Arch. 2021 Aug;473(8):1273-1285. doi: 10.1007/s00424-021-02592-5. Epub 2021 Jul 6.
5
High and synergistic activity between mTORC1 and PLK1 inhibition in adenocarcinoma NSCLC.mTORC1与PLK1抑制在非小细胞肺癌腺癌中具有高度协同活性。
Oncotarget. 2021 Apr 13;12(8):859-872. doi: 10.18632/oncotarget.27930.
6
CDK5RAP3 inhibits angiogenesis in gastric neuroendocrine carcinoma by modulating AKT/HIF-1α/VEGFA signaling.CDK5RAP3通过调节AKT/HIF-1α/VEGFA信号通路抑制胃神经内分泌癌的血管生成。
Cancer Cell Int. 2019 Nov 7;19:282. doi: 10.1186/s12935-019-0997-5. eCollection 2019.
7
Topiramate exhibits anti-tumorigenic and metastatic effects in ovarian cancer cells.托吡酯在卵巢癌细胞中表现出抗肿瘤和转移作用。
Am J Transl Res. 2018 Jun 15;10(6):1663-1676. eCollection 2018.
8
Lactate stimulates CA IX expression in normoxic cancer cells.乳酸刺激常氧癌细胞中碳酸酐酶IX（CA IX）的表达。
Oncotarget. 2017 Sep 12;8(44):77819-77835. doi: 10.18632/oncotarget.20836. eCollection 2017 Sep 29.
9
Eukaryotic Translation Initiation Factor 3b is both a Promising Prognostic Biomarker and a Potential Therapeutic Target for Patients with Clear Cell Renal Cell Carcinoma.真核生物翻译起始因子3b既是透明细胞肾细胞癌患者有前景的预后生物标志物，也是潜在的治疗靶点。
J Cancer. 2017 Sep 2;8(15):3049-3061. doi: 10.7150/jca.19594. eCollection 2017.
10
Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies.头颈部鳞状细胞癌和非小细胞肺癌中缺氧、AKT与HIF-1信号通路之间的相互作用：对未来治疗策略的启示
Future Sci OA. 2016 Jan 29;2(1):FSO84. doi: 10.4155/fso.15.84. eCollection 2016 Mar.
本文引用的文献
1
Distinct thresholds govern Myc's biological output in vivo.不同的阈值在体内调控Myc的生物学效应。
Cancer Cell. 2008 Dec 9;14(6):447-57. doi: 10.1016/j.ccr.2008.10.018.
2
PTEN and the PI3-kinase pathway in cancer.癌症中的PTEN与PI3激酶信号通路
Annu Rev Pathol. 2009;4:127-50. doi: 10.1146/annurev.pathol.4.110807.092311.
3
The human side of hypoxia-inducible factor.缺氧诱导因子的人文因素
Br J Haematol. 2008 May;141(3):325-34. doi: 10.1111/j.1365-2141.2008.07029.x.
4
AKT signaling in regulating angiogenesis.AKT信号传导在调节血管生成中的作用。
Curr Cancer Drug Targets. 2008 Feb;8(1):19-26. doi: 10.2174/156800908783497122.
5
A hypoxia-independent up-regulation of hypoxia-inducible factor-1 by AKT contributes to angiogenesis in human gastric cancer.AKT对缺氧诱导因子-1的非缺氧依赖性上调促进了人胃癌的血管生成。
Carcinogenesis. 2008 Jan;29(1):44-51. doi: 10.1093/carcin/bgm232. Epub 2007 Nov 4.
6
Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases.I类磷脂酰肌醇3激酶强效抑制剂的药理学特性
Cancer Res. 2007 Jun 15;67(12):5840-50. doi: 10.1158/0008-5472.CAN-06-4615.
7
Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1alpha and Sp1 through the phosphatidylinositol 3-kinase/Akt signaling pathway.缺氧条件和高细胞密度诱导的Redd1表达是通过磷脂酰肌醇3-激酶/蛋白激酶B信号通路，由缺氧诱导因子-1α和Sp1的激活来调控的。
Cell Signal. 2007 Jul;19(7):1393-403. doi: 10.1016/j.cellsig.2006.12.014. Epub 2007 Jan 20.
8
Hypoxia-independent overexpression of hypoxia-inducible factor 1alpha as an early change in mouse hepatocarcinogenesis.缺氧诱导因子1α的非缺氧依赖性过表达作为小鼠肝癌发生的早期变化。
Cancer Res. 2006 Dec 1;66(23):11263-70. doi: 10.1158/0008-5472.CAN-06-1699.
9
Akt1 activation can augment hypoxia-inducible factor-1alpha expression by increasing protein translation through a mammalian target of rapamycin-independent pathway.Akt1激活可通过不依赖雷帕霉素哺乳动物靶点的途径增加蛋白质翻译，从而增强缺氧诱导因子-1α的表达。
Mol Cancer Res. 2006 Jul;4(7):471-9. doi: 10.1158/1541-7786.MCR-05-0234.
10
Proteasomal inhibition attenuates transcriptional activity of hypoxia-inducible factor 1 (HIF-1) via specific effect on the HIF-1alpha C-terminal activation domain.蛋白酶体抑制通过对缺氧诱导因子1（HIF-1）α C末端激活域的特异性作用减弱缺氧诱导因子1（HIF-1）的转录活性。
Mol Cell Biol. 2006 Aug;26(15):5895-907. doi: 10.1128/MCB.00552-06.
Zotero 插件