Home LiteratureArticle Details
PMID: 23999440 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations.

The Journal of clinical investigation ·Vol. 123 ·No. 9 ·2013-09-00 ·Pages 3664-71

Semenza GL

Abstract

Hypoxia occurs frequently in human cancers and induces adaptive changes in cell metabolism that include a switch from oxidative phosphorylation to glycolysis, increased glycogen synthesis, and a switch from glucose to glutamine as the major substrate for fatty acid synthesis. This broad metabolic reprogramming is coordinated at the transcriptional level by HIF-1, which functions as a master regulator to balance oxygen supply and demand. HIF-1 is also activated in cancer cells by tumor suppressor (e.g., VHL) loss of function and oncogene gain of function (leading to PI3K/AKT/mTOR activity) and mediates metabolic alterations that drive cancer progression and resistance to therapy. Inhibitors of HIF-1 or metabolic enzymes may impair the metabolic flexibility of cancer cells and make them more sensitive to anticancer drugs.

MeSH Terms
Adaptation, Physiological Animals Cell Hypoxia Drug Resistance, Neoplasm Energy Metabolism Humans Hypoxia-Inducible Factor 1, alpha Subunit/physiology Mutation Neoplasms/drug therapy,genetics,metabolism,pathology Oncogenes
Chemicals
HIF1A protein, human Hypoxia-Inducible Factor 1, alpha Subunit
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Semenza Gregg L
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
References (114)
114 references, click to expand
  1. From polyps to people: a highly familiar response to hypoxia.
    Ann N Y Acad Sci. 2009 Oct;1177:19-29 PMID: 19845603
  2. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase.
    Mol Cell. 2012 Mar 9;45(5):598-609 PMID: 22306293
  3. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells.
    Cell Stem Cell. 2013 Mar 7;12(3):329-41 PMID: 23333149
  4. Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.
    Genes Dev. 2000 Jan 1;14(1):34-44 PMID: 10640274
  5. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics.
    Cancer Res. 2000 Mar 15;60(6):1541-5 PMID: 10749120
  6. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1.
    Mol Cell Biol. 1996 Sep;16(9):4604-13 PMID: 8756616
  7. Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth.
    Sci Signal. 2009 Nov 17;2(97):ra73 PMID: 19920251
  8. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.
    Nature. 1999 May 20;399(6733):271-5 PMID: 10353251
  9. V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression.
    Cancer Res. 1997 Dec 1;57(23):5328-35 PMID: 9393757
  10. Loss of PTEN facilitates HIF-1-mediated gene expression.
    Genes Dev. 2000 Feb 15;14(4):391-6 PMID: 10691731
  11. miR-210: More than a silent player in hypoxia.
    IUBMB Life. 2011 Feb;63(2):94-100 PMID: 21360638
  12. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases.
    Nat Rev Drug Discov. 2011 Jun;10(6):417-27 PMID: 21629292
  13. Glucose utilization via glycogen phosphorylase sustains proliferation and prevents premature senescence in cancer cells.
    Cell Metab. 2012 Dec 5;16(6):751-64 PMID: 23177934
  14. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase.
    Cancer Cell. 2005 Jan;7(1):77-85 PMID: 15652751
  15. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains.
    Mol Cell Biol. 2009 May;29(10):2570-81 PMID: 19273585
  16. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism.
    Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1894-9 PMID: 20133837
  17. HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors.
    Cancer Res. 2001 Sep 15;61(18):6669-73 PMID: 11559532
  18. Glycolytic enzymes can modulate cellular life span.
    Cancer Res. 2005 Jan 1;65(1):177-85 PMID: 15665293
  19. Tumor hypoxia and malignant progression.
    Methods Enzymol. 2004;381:335-54 PMID: 15063685
  20. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia.
    Nature. 2011 Nov 20;481(7381):380-4 PMID: 22101433
  21. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.
    Cancer Cell. 2007 Jan;11(1):37-51 PMID: 17222789
  22. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases.
    Cancer Res. 1999 Nov 15;59(22):5830-5 PMID: 10582706
  23. Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis.
    Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4260-5 PMID: 19255431
  24. Dichloroacetate reverses the hypoxic adaptation to bevacizumab and enhances its antitumor effects in mouse xenografts.
    J Mol Med (Berl). 2013 Jun;91(6):749-58 PMID: 23361368
  25. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4 PMID: 7539918
  26. Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1alpha.
    Blood. 1998 Oct 1;92(7):2260-8 PMID: 9746763
  27. Mitochondrial activation by inhibition of PDKII suppresses HIF1a signaling and angiogenesis in cancer.
    Oncogene. 2013 Mar 28;32(13):1638-50 PMID: 22614004
  28. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth.
    Nature. 2008 Mar 13;452(7184):230-3 PMID: 18337823
  29. HIF1α is required for survival maintenance of chronic myeloid leukemia stem cells.
    Blood. 2012 Mar 15;119(11):2595-607 PMID: 22275380
  30. HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron.
    Cancer Cell. 2002 Jun;1(5):459-68 PMID: 12124175
  31. Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins.
    Nat Struct Mol Biol. 2012 Feb 05;19(3):346-54 PMID: 22307054
  32. Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia.
    J Biol Chem. 2008 Apr 18;283(16):10892-903 PMID: 18281291
  33. Pyruvate kinase M2 is a phosphotyrosine-binding protein.
    Nature. 2008 Mar 13;452(7184):181-6 PMID: 18337815
  34. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
    Mol Cell. 2008 May 23;30(4):393-402 PMID: 18498744
  35. Signal transduction by reactive oxygen species.
    J Cell Biol. 2011 Jul 11;194(1):7-15 PMID: 21746850
  36. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1.
    Blood. 2005 Jan 15;105(2):659-69 PMID: 15374877
  37. The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis.
    Genes Dev. 2007 May 1;21(9):1037-49 PMID: 17437992
  38. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells.
    Cell. 2007 Apr 6;129(1):111-22 PMID: 17418790
  39. HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression.
    Nat Rev Cancer. 2011 Dec 15;12(1):9-22 PMID: 22169972
  40. Hypoxia response and microRNAs: no longer two separate worlds.
    J Cell Mol Med. 2008 Sep-Oct;12(5A):1426-31 PMID: 18624759
  41. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible.
    Science. 2013 Mar 29;339(6127):1621-5 PMID: 23393090
  42. Tumor-associated carbonic anhydrase 9 spatially coordinates intracellular pH in three-dimensional multicellular growths.
    J Biol Chem. 2008 Jul 18;283(29):20473-83 PMID: 18482982
  43. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2.
    Cell Metab. 2009 Oct;10(4):273-84 PMID: 19808020
  44. Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation.
    Nature. 2011 Dec 1;480(7375):118-22 PMID: 22056988
  45. Glycolysis in chick embryo cell cultures transformed by Rous sarcoma virus.
    Cancer Res. 1968 Aug;28(8):1611-9 PMID: 4299826
  46. Metabolic associations of reduced proliferation and oxidative stress in advanced breast cancer.
    Cancer Res. 2012 Nov 15;72(22):5712-20 PMID: 22986741
  47. Mxi1 is induced by hypoxia in a HIF-1-dependent manner and protects cells from c-Myc-induced apoptosis.
    Cancer Biol Ther. 2005 Nov;4(11):1285-94 PMID: 16319523
  48. Purification and characterization of hypoxia-inducible factor 1.
    J Biol Chem. 1995 Jan 20;270(3):1230-7 PMID: 7836384
  49. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation.
    Nature. 2012 Feb 15;483(7390):484-8 PMID: 22343896
  50. Metabolomic changes accompanying transformation and acquisition of metastatic potential in a syngeneic mouse mammary tumor model.
    J Biol Chem. 2010 Mar 26;285(13):9317-9321 PMID: 20139083
  51. MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors.
    Nat Genet. 2013 Jan;45(1):104-8 PMID: 23202129
  52. HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs.
    Oncogene. 2012 Apr 5;31(14):1757-70 PMID: 21860410
  53. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing.
    J Biol Chem. 2000 Aug 18;275(33):25130-8 PMID: 10833514
  54. Hypoxia promotes glycogen accumulation through hypoxia inducible factor (HIF)-mediated induction of glycogen synthase 1.
    PLoS One. 2010 Mar 12;5(3):e9644 PMID: 20300197
  55. Induction of pyruvate dehydrogenase kinase-3 by hypoxia-inducible factor-1 promotes metabolic switch and drug resistance.
    J Biol Chem. 2008 Oct 17;283(42):28106-14 PMID: 18718909
  56. Serine is a natural ligand and allosteric activator of pyruvate kinase M2.
    Nature. 2012 Nov 15;491(7424):458-462 PMID: 23064226
  57. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression.
    Mol Cell Biol. 2001 Jun;21(12):3995-4004 PMID: 11359907
  58. Hypoxia-inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis.
    J Clin Invest. 2013 Jan;123(1):189-205 PMID: 23318994
  59. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice.
    J Clin Invest. 2008 Dec;118(12):3930-42 PMID: 19033663
  60. HIF-1alpha and HIF-2alpha have divergent roles in colon cancer.
    Int J Cancer. 2009 Feb 15;124(4):763-71 PMID: 19030186
  61. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis.
    Nat Genet. 2011 Jul 31;43(9):869-74 PMID: 21804546
  62. Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha.
    Genes Dev. 1998 Jan 15;12(2):149-62 PMID: 9436976
  63. Applying the discovery of the Philadelphia chromosome.
    J Clin Invest. 2007 Aug;117(8):2067-74 PMID: 17671641
  64. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth.
    Cancer Cell. 2012 Nov 13;22(5):585-600 PMID: 23153533
  65. The pharmacology of dichloroacetate.
    Metabolism. 1989 Nov;38(11):1124-44 PMID: 2554095
  66. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer.
    Nat Rev Cancer. 2008 Nov;8(11):865-73 PMID: 18923434
  67. HIF-1alpha induces cell cycle arrest by functionally counteracting Myc.
    EMBO J. 2004 May 5;23(9):1949-56 PMID: 15071503
  68. A nontranscriptional role for HIF-1α as a direct inhibitor of DNA replication.
    Sci Signal. 2013 Feb 12;6(262):ra10 PMID: 23405012
  69. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling.
    Cardiovasc Res. 2010 May 1;86(2):236-42 PMID: 20164116
  70. MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU.
    PLoS One. 2010 Apr 26;5(4):e10345 PMID: 20436681
  71. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.
    Nature. 2010 Jan 21;463(7279):364-8 PMID: 20010808
  72. Target gene selectivity of hypoxia-inducible factor-alpha in renal cancer cells is conveyed by post-DNA-binding mechanisms.
    Br J Cancer. 2007 Apr 23;96(8):1284-92 PMID: 17387348
  73. Genome-wide association of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha DNA binding with expression profiling of hypoxia-inducible transcripts.
    J Biol Chem. 2009 Jun 19;284(25):16767-16775 PMID: 19386601
  74. Alterations in glucose metabolism in chick-embryo cells transformed by Rous sarcoma virus: intracellular levels of glycolytic intermediates.
    Proc Natl Acad Sci U S A. 1974 Oct;71(10):4129-32 PMID: 4372608
  75. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses.
    Science. 2011 Dec 2;334(6060):1278-83 PMID: 22052977
  76. Cellular adaptations to hypoxia and acidosis during somatic evolution of breast cancer.
    Br J Cancer. 2007 Sep 3;97(5):646-53 PMID: 17687336
  77. Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition.
    Mol Cancer Ther. 2009 Jul;8(7):1867-77 PMID: 19584228
  78. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children.
    Pediatrics. 2006 May;117(5):1519-31 PMID: 16651305
  79. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption.
    Cell Metab. 2006 Mar;3(3):187-97 PMID: 16517406
  80. The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type.
    Cell Metab. 2012 Feb 8;15(2):157-70 PMID: 22326218
  81. Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons.
    J Mol Cell Biol. 2012 Apr;4(2):79-87 PMID: 22044881
  82. Role of monocarboxylate transporters in human cancers: state of the art.
    J Bioenerg Biomembr. 2012 Feb;44(1):127-39 PMID: 22407107
  83. Reversion of transformed glycolysis to normal by inhibition of protein synthesis in rat kidney cells infected with temperature-sensitive mutant of Rous sarcoma virus.
    Proc Natl Acad Sci U S A. 1978 Oct;75(10):5015-9 PMID: 217010
  84. Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia.
    Nat Cell Biol. 2007 Feb;9(2):210-7 PMID: 17220880
  85. The bioenergetic signature of cancer: a marker of tumor progression.
    Cancer Res. 2002 Nov 15;62(22):6674-81 PMID: 12438266
  86. HIF-dependent antitumorigenic effect of antioxidants in vivo.
    Cancer Cell. 2007 Sep;12(3):230-8 PMID: 17785204
  87. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1.
    Cell. 2011 May 27;145(5):732-44 PMID: 21620138
  88. Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription.
    Int J Biochem Cell Biol. 2008;40(5):1043-54 PMID: 18191611
  89. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1.
    J Biol Chem. 1996 Dec 20;271(51):32529-37 PMID: 8955077
  90. HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability.
    Cancer Cell. 2005 Aug;8(2):143-53 PMID: 16098467
  91. Dynamic change of chromatin conformation in response to hypoxia enhances the expression of GLUT3 (SLC2A3) by cooperative interaction of hypoxia-inducible factor 1 and KDM3A.
    Mol Cell Biol. 2012 Aug;32(15):3018-32 PMID: 22645302
  92. Imatinib resistance associated with BCR-ABL upregulation is dependent on HIF-1alpha-induced metabolic reprograming.
    Oncogene. 2010 May 20;29(20):2962-72 PMID: 20228846
  93. Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis.
    J Mol Med (Berl). 2012 Jul;90(7):803-15 PMID: 22231744
  94. SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions.
    Science. 2012 Nov 23;338(6110):1069-72 PMID: 23086999
  95. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq.
    Blood. 2011 Jun 9;117(23):e207-17 PMID: 21447827
  96. Metabolic modulation of glioblastoma with dichloroacetate.
    Sci Transl Med. 2010 May 12;2(31):31ra34 PMID: 20463368
  97. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1alpha.
    Science. 2009 Apr 10;324(5924):261-5 PMID: 19359588
  98. Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer.
    J Cell Mol Med. 2010 Apr;14(4):771-94 PMID: 20015196
  99. Molecular mechanisms mediating metastasis of hypoxic breast cancer cells.
    Trends Mol Med. 2012 Sep;18(9):534-43 PMID: 22921864
  100. HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity.
    Cancer Cell. 2007 May;11(5):407-20 PMID: 17482131
  101. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin.
    Mol Cell Biol. 2002 Oct;22(20):7004-14 PMID: 12242281
  102. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia.
    Cell Metab. 2006 Mar;3(3):177-85 PMID: 16517405
  103. The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens.
    EMBO Rep. 2011 Jan;12(1):63-70 PMID: 21109780
  104. Regulation of cancer cell metabolism by hypoxia-inducible factor 1.
    Semin Cancer Biol. 2009 Feb;19(1):12-6 PMID: 19114105
  105. Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations.
    Hum Mol Genet. 2005 Aug 1;14(15):2231-9 PMID: 15987702
  106. Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability.
    Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19611-6 PMID: 22106302
  107. Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma.
    Cancer. 2013 Apr 15;119(8):1547-54 PMID: 23335244
  108. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics.
    Oncogene. 2010 Feb 4;29(5):625-34 PMID: 19946328
  109. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.
    Genes Dev. 1997 Jan 1;11(1):72-82 PMID: 9000051
  110. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells.
    Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):E2707-16 PMID: 23012449
  111. Metabolic regulation of hematopoietic stem cells in the hypoxic niche.
    Cell Stem Cell. 2011 Oct 4;9(4):298-310 PMID: 21982230
  112. BCR/ABL induces expression of vascular endothelial growth factor and its transcriptional activator, hypoxia inducible factor-1alpha, through a pathway involving phosphoinositide 3-kinase and the mammalian target of rapamycin.
    Blood. 2002 Nov 15;100(10):3767-75 PMID: 12393646
  113. The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages.
    Am J Pathol. 2000 Aug;157(2):411-21 PMID: 10934146
  114. Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.
    Mol Cell. 2011 Jun 24;42(6):719-30 PMID: 21700219
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
1558-8238
DOI
10.1172/JCI67230
Published
2013-09-00
Epub
2013-00-03
Pages
3664-71
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC3754249
Subset
IM
Grants
NCI NIH HHS · U54 CA143868 · United States
NCI NIH HHS · U54-CA143868 · United States
PHS HHS · HHS-N268201000032C · United States
External Links
PubMed source DOI: 10.1172/JCI67230 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2