欢迎来到《四川大学学报(医学版)》

高原低氧适应与低氧实体瘤

吴奇胜 刘培燊 杨翠萍 陈勇彬

吴奇胜, 刘培燊, 杨翠萍, 等. 高原低氧适应与低氧实体瘤[J]. 四川大学学报(医学版), 2021, 52(1): 50-56. doi: 10.12182/20210160504
引用本文: 吴奇胜, 刘培燊, 杨翠萍, 等. 高原低氧适应与低氧实体瘤[J]. 四川大学学报(医学版), 2021, 52(1): 50-56. doi: 10.12182/20210160504
WU Qi-sheng, LIU Pei-shen, YANG Cui-ping, et al. A Review of High-altitude Hypoxia Adaptation and Hypoxic Solid Tumor[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 50-56. doi: 10.12182/20210160504
Citation: WU Qi-sheng, LIU Pei-shen, YANG Cui-ping, et al. A Review of High-altitude Hypoxia Adaptation and Hypoxic Solid Tumor[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 50-56. doi: 10.12182/20210160504

栏目: 综 述

高原低氧适应与低氧实体瘤

doi: 10.12182/20210160504
基金项目: 国家自然科学基金(No. 81772996、No. 81672764、No. U1902216)资助
详细信息
    作者简介:

    陈勇彬,研究员,现任中科院昆明动物研究所肿瘤信号转导研究组负责人。研究方向:肿瘤发生机制;干细胞多能性维持;抗肿瘤及提高干细胞功能新药筛选。2005年在中科院上海生化与细胞研究所获理学博士学位。2005−2012年在美国德州西南医学中心先后作为博士后和研究助理从事肿瘤与干细胞信号转导通路研究工作。2012年回中科院昆明动物研究所,成立肿瘤信号转导研究课题组。曾获云南省科技进步(特等奖、一等奖)等奖励,第七届云南省青年科技奖。在国际主流杂志发表论著20余篇。已获国家自然科学基金委优秀青年科学基金、国家自然科学基金面上项目、国家重点基础研究发展计划(973计划)项目(课题骨干1项)等多个项目资助。兼任中国抗癌协会肿瘤标志物专委会青年副主委,中国抗癌协会、细胞生物学会、病理生理学会和遗传学会常务青年委员(理事),云南省骨肉瘤专业委员会副主任委员等

    通讯作者:

    E-mail: ybchen@mail.kiz.ac.cn

A Review of High-altitude Hypoxia Adaptation and Hypoxic Solid Tumor

More Information
  • 摘要: 寒武纪生命大爆发是一次由于环境氧浓度改变而导致的重大生命演化事件。对氧气的利用是高等生命赖以生存的本能,并因此进化出了复杂的调节系统来应对环境中氧气浓度的变化。低氧是高原环境的典型特点之一,通过高原低氧环境的长期自然选择,生活在高原地区的许多物种都演化出了独特的低氧适应机制。高原低氧环境中各种生物通过自然选择而实现的低氧适应过程与各种人类实体瘤中的肿瘤细胞低氧适应性状高度相似,本文从高原生物和实体瘤细胞的低氧适应性进化两个方面进行总结与讨论,以期通过对高原低氧适应性进化的分子机制进行深入解析,为低氧适应新基因的筛选和低氧实体瘤发生发展的分子机制解析提供新的研究策略。
  • [1] 朱茂炎, 赵方臣, 殷宗军, 等. 中国的寒武纪大爆发研究: 进展与展望. 中国科学: 地球科学,2019,49(10): 1455–1490. doi: 10.1007/s11430-019-9508-4
    [2] FOX D. What sparked the Cambrian explosion? Nature,2016,530(7590): 268–270. doi: 10.1038/530268a
    [3] IVAN M, KAELIN W G, Jr. The EGLN-HIF O(2)-sensing system: multiple inputs and feedbacks. Mol Cel,2017,66(6): 772–779. doi: 10.1016/j.molcel.2017.06.002
    [4] SEMENZA G L, RUE E A, IYER N V, et al. Assignment of the hypoxia-inducible factor 1alpha gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14q. Genomics,1996,34(3): 437–439. doi: 10.1006/geno.1996.0311
    [5] WU T Y. Life on the high Tibetan plateau. High Alt Med Biol,2004,5(1): 1–2. doi: 10.1089/152702904322963609
    [6] QI X, CUI C, PENG Y, et al. Genetic evidence of paleolithic colonization and neolithic expansion of modern humans on the tibetan plateau. Mol Biol Evol, 2013, 30(8): 1761-1778.
    [7] 吴天一. 高原低氧环境对人类的挑战. 医学研究杂志,2006(10): 1–3.
    [8] KAPPLER M, TAUBERT H , ECKERT A W. Oxygen sensing, homeostasis, and disease. N Engl J med,2011,365(6): 537–547. doi: 10.1056/NEJMc1110602
    [9] CAIRNS R A, HARRIS I S, MAK T W. Regulation of cancer cell metabolism. Nat Rev Cancer,2011,11(2): 85–95.
    [10] JING X, YANG F, SHAO C, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer,2019,18(1): 157[2020-12-15].https://doi.org/10.1186/s12943-019-1089-9. doi: 10.1186/s12943-019-1089-9
    [11] GILKES D M, SEMENZA G L, WIRTZ D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer,2014,14(6): 430–439. doi: 10.1038/nrc3726
    [12] BEALL C M. Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proc Nati Acad Sci U S A,2007,104(Suppl 1): 8655–8660. doi: 10.1073/pnas.0701985104
    [13] CHIRAT R, MOULTON D E, GORIELY A. Mechanical basis of morphogenesis and convergent evolution of spiny seashells. Proc Nati Acad Sci U S A,2013,110(15): 6015–6020. doi: 10.1073/pnas.1220443110
    [14] 张天留, 高雪, 徐凌洋, 等. 高原家养动物环境适应性的研究进展. 畜牧兽医学报,2020,51(7): 1475–1487.
    [15] FENG S, MA J, LONG K, et al. Comparative microRNA Transcriptomes in domestic goats reveal acclimatization to high altitude. Front Genet, 2020, 11: 809[2020-12-15]. https://doi.org/10.3389/fgene.2020.00809.
    [16] THIERSCH M, SWENSON E R. High altitude and cancer mortality. High Alt Med Biol,2018,19(2): 116–123. doi: 10.1089/ham.2017.0061
    [17] ZHOU M, WANG H, ZHU J, et al. Cause-specific mortality for 240 causes in China during 1990-2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet,2016,387(10015): 251–272. doi: 10.1016/S0140-6736(15)00551-6
    [18] BAKER P T, LITTLE M A. Man in the Andes. Stroudsburg: Dowden, Hutchinson & Ross, 1976.
    [19] COSIO G. Hematic and cardiopulmonary characteristics of the Andean miner. Bol Oficina Sanit Panam,1972,72(6): 547–557.
    [20] BEALL C M. Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia. Integr Comp Biol,2006,46(1): 18–24. doi: 10.1093/icb/icj004
    [21] GARRUTO R M, CHIN C T, WEITZ C A, et al. Hematological differences during growth among Tibetans and Han Chinese born and raised at high altitude in Qinghai, China. Am J Phys Anthropol,2003,122(2): 171–183. doi: 10.1002/ajpa.10283
    [22] BEALL C M, SONG K, ELSTON R C, et al. Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4 000 m. Proc Nati Acad Sci U S A,2004,101(39): 14300–14304. doi: 10.1073/pnas.0405949101
    [23] UDPA N, RONEN R, ZHOU D, et al. Whole genome sequencing of Ethiopian highlanders reveals conserved hypoxia tolerance genes. Genome Biol,2014,15(2): R36[2020-12-15]. https://doi.org/10.1186/gb-2014-15-2-r36. doi: 10.1186/gb-2014-15-2-r36
    [24] LEE P, CHANDEL N S, SIMON M C. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol,2020,21(5): 268–283. doi: 10.1038/s41580-020-0227-y
    [25] XIONG Q, LIU B, DING M, et al. Hypoxia and cancer related pathology. Cancer Lett,2020,486: 1–7. doi: 10.1016/j.canlet.2020.05.002
    [26] CAMUZI D, DE AMORIM Í S S, RIBEIRO PINTO L F, et al. Regulation is in the air: the relationship between hypoxia and epigenetics in cancer. Cells, 2019, 8(4): 300[2020-12-15]. https://doi.org/10.3390/cells8040300.
    [27] RANKIN E B, GIACCIA A J. Hypoxic control of metastasis. Science,2016,352(6282): 175–180. doi: 10.1126/science.aaf4405
    [28] SULLIVAN L B, GUI D Y, VANDER HEIDEN M G. Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. Nat Rev Cancer,2016,16(11): 680–693. doi: 10.1038/nrc.2016.85
    [29] PAVLOVA N N, THOMPSON C B. The emerging hallmarks of cancer metabolism. Cell Metab,2016,23(1): 27–47. doi: 10.1016/j.cmet.2015.12.006
    [30] FAUBERT B, LI K Y, CAI L, et al. Lactate metabolism in human lung tumors. Cell,2017,171(2): 358–371. doi: 10.1016/j.cell.2017.09.019
    [31] VAUPEL P, SCHLENGER K, KNOOP C, et al. Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res,1991,51(12): 3316–3322.
    [32] VANDER HEIDEN M G, CANTLEY L C, THOMPSON C B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science,2009,324(5930): 1029–1033. doi: 10.1126/science.1160809
    [33] BÖHME I, BOSSERHOFF A K. Acidic tumor microenvironment in human melanoma. Pigment Cell Melanoma Res,2016,29(5): 508–523. doi: 10.1111/pcmr.12495
    [34] SEMENZA G L, NEJFELT M K, CHI S M, et al. Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene. Proc NatiAcad Sci U S A,1991,88(13): 5680–5684. doi: 10.1073/pnas.88.13.5680
    [35] IVAN M, KONDO K, YANG H, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science,2001,292(5516): 464–468. doi: 10.1126/science.1059817
    [36] JAAKKOLA P, MOLE D R, TIAN Y M, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science,2001,292(5516): 468–472. doi: 10.1126/science.1059796
    [37] THOMPSON C B. Into thin air: how we sense and respond to hypoxia. Cell,2016,167(1): 9–11. doi: 10.1016/j.cell.2016.08.036
    [38] GOEL H L, MERCURIO A M. VEGF targets the tumour cell. Nat Rev Cancer,2013,13(12): 871–882. doi: 10.1038/nrc3627
    [39] SANG N, STIEHL D P, BOHENSKY J, et al. MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300. J Biol Chem,2003,278(16): 14013–14019. doi: 10.1074/jbc.M209702200
    [40] FORSYTHE J A, JIANG B H, IYER N V, et al. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol,1996,16(9): 4604–4613. doi: 10.1128/mcb.16.9.4604
    [41] MAK P, LEAV I, PURSELL B, et al. ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell,2010,17(4): 319–332. doi: 10.1016/j.ccr.2010.02.030
    [42] ZHU J, THOMPSON C B. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol,2019,20(7): 436–450. doi: 10.1038/s41580-019-0123-5
    [43] GODET I, SHIN Y J, JU J A, et al. Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nat Commun,2019,10(1): 4862[2020-12-15]. https://doi.org/10.1038/s41467-019-12412-1. doi: 10.1038/s41467-019-12412-1
    [44] SHI Y, FAN S, WU M, et al. YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat Commun,2019,10(1): 4892[2020-12-15]. https://doi.org/10.1038/s41467-019-12801-6. doi: 10.1038/s41467-019-12801-6
    [45] PRASAD S, GUPTA S C, TYAGI A K. Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals. Cancer Lett,2017,387: 95–105. doi: 10.1016/j.canlet.2016.03.042
    [46] CHANDEL N S. Mitochondrial complex Ⅲ: an essential component of universal oxygen sensing machinery? Respir Physiol Neurobiol,2010,174(3): 175–181. doi: 10.1016/j.resp.2010.08.004
    [47] PAULSEN C E, CARROLL K S. Cysteine-mediated redox signaling: chemistry, biology, and tools for discovery. Chem Rev,2013,113(7): 4633–4679. doi: 10.1021/cr300163e
    [48] KOBAYASHI M, YAMAMOTO M. Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Adv Enzyme Regul,2006,46: 113–140. doi: 10.1016/j.advenzreg.2006.01.007
    [49] KLAUNIG J E, XU Y, ISENBERG J S, et al. The role of oxidative stress in chemical carcinogenesis. Environ Health Perspect,1998,106(Suppl 1): 289–295. doi: 10.1289/ehp.98106s1289
    [50] ZHOU L, ZHANG Z, HUANG Z, et al. Revisiting cancer hallmarks: insights from the interplay between oxidative stress and non-coding RNAs. Mol Biom,2020,1(1): 4[2020-12-15]. https://doi.org/10.1186/s43556-020-00004-1. doi: 10.1186/s43556-020-00004-1
    [51] ZHANG J, WANG X, VIKASH V, et al. ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev,2016,2016: 4350965[2020-12-11]. https://doi.org/10.1155/2016/4350965. doi: 10.1155/2016/4350965
    [52] MAULIK N, DAS D K. Redox signaling in vascular angiogenesis. Free Radic Biol Med,2002,33(8): 1047–1060. doi: 10.1016/s0891-5849(02)01005-5
    [53] SHIMOJO Y, AKIMOTO M, HISANAGA T, et al. Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells. Clin Exp Metastasis,2013,30(2): 143–154. doi: 10.1007/s10585-012-9519-8
    [54] LIU Y, GUO J Z, LIU Y, et al. Nuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth. Nat Commun,2018,9(1): 4429[2020-12-15]. https://doi.org/10.1038/s41467-018-06841-7. doi: 10.1038/s41467-018-06841-7
    [55] HEGDE P S, CHEN D S. Top 10 challenges in cancer immunotherapy. Immunity,2020,52(1): 17–35. doi: 10.1016/j.immuni.2019.12.011
    [56] PALAZON A, GOLDRATH A W, NIZET V, et al. HIF transcription factors, inflammation, and immunity. Immunity,2014,41(4): 518–528. doi: 10.1016/j.immuni.2014.09.008
    [57] RENNER K, SINGER K, KOEHL G E, et al. Metabolic hallmarks of tumor and immune cells in the tumor microenvironment. Front Immunol,2017,8: 248[2020-12-15]. https://doi.org/10.3389/fimmu.2017.00248. doi: 10.3389/fimmu.2017.00248
    [58] PALAZON A, TYRAKIS P A, MACIAS D, et al. An HIF-1α/VEGF-A axis in cytotoxic T cells regulates tumor progression. Cancer Cell,2017,32(5): 669–683. doi: 10.1016/j.ccell.2017.10.003
    [59] KRZYWINSKA E, KANTARI-MIMOUN C, KERDILES Y, et al. Loss of HIF-1α in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis. Nat Commun,2017,8(1): 1597[2020-12-15].https://doi.org/10.1038/s41467-017-01599-w. doi: 10.1038/s41467-017-01599-w
    [60] WENES M, SHANG M, DI MATTEO M, et al. Macrophage metabolism controls tumor blood vessel morphogenesis and metastasis. Cell Metab,2016,24(5): 701–715. doi: 10.1016/j.cmet.2016.09.008
    [61] ANDO N, HARA M, SHIGA K, et al. Eicosapentaenoic acid suppresses angiogenesis via reducing secretion of IL-6 and VEGF from colon cancer-associated fibroblasts. Oncol Rep,2019,42(1): 339–349. doi: 10.3892/or.2019.7141
    [62] LIU N, LUO J, KUANG D, et al. Lactate inhibits ATP6V0d2 expression in tumor-associated macrophages to promote HIF-2α-mediated tumor progression. J Clin Invest,2019,129(2): 631–646. doi: 10.1172/JCI123027
    [63] CLEVER D, ROYCHOUDHURI R, CONSTANTINIDES M G, et al. Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche. Cell,2016,166(5): 1117–1131. doi: 10.1016/j.cell.2016.07.032
    [64] JOHNSTON R J, SU L J, PINCKNEY J, et al. VISTA is an acidic pH-selective ligand for PSGL-1. Nature,2019,574(7779): 565–570. doi: 10.1038/s41586-019-1674-5
    [65] XIN J, ZHANG H, HE Y, et al. Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation. Nat Commun,2020,11(1): 4928[2020-12-15].https://doi.org/10.1038/s41467-020-18638-8. doi: 10.1038/s41467-020-18638-8
    [66] LI Y, WANG M S, OTECKO N O, et al. Hypoxia potentially promotes Tibetan longevity. Cell Res,2017,27(2): 302–305. doi: 10.1038/cr.2016.105
    [67] LI Y, WU D D, BOYKO A R, et al. Population variation revealed high-altitude adaptation of Tibetan mastiffs. Mol Biol Evol,2014,31(5): 1200–1205. doi: 10.1093/molbev/msu070
    [68] PENG Y, CUI C, HE Y, et al. Down-regulation of EPAS1 transcription and genetic adaptation of tibetans to high-altitude hypoxia. Mol Biol Evol,2017,34(4): 818–830. doi: 10.1093/molbev/msw280
    [69] XU X H, BAO Y, WANG X, et al. Hypoxic-stabilized EPAS1 proteins transactivate DNMT1 and cause promoter hypermethylation and transcription inhibition of EPAS1 in non-small cell lung cancer. FASEB J,2018,32(12): fj201700715[2020-12-15]. https://doi.org/10.1096/fj.201700715. doi: 10.1096/fj.201700715
    [70] 陈丽华, 朱婕曼, 刘玉凤, 等. miR-34、MDM2、EPAS1在子宫内膜癌中的表达及与临床特征的相关性分析. 解放军医药杂志,2020,32(7): 38–42.
    [71] SIMONSON T S, YANG Y, HUFF C D, et al. Genetic evidence for high-altitude adaptation in Tibet. Science,2010,329(5987): 72–75. doi: 10.1126/science.1189406
    [72] LI Z, ZHOU W, ZHANG Y, et al. ERK Regulates HIF1α-mediated platinum resistance by directly targeting PHD2 in ovarian cancer. Clin Can Res,2019,25(19): 5947–5960. doi: 10.1158/1078-0432.CCR-18-4145
    [73] CAO Y, LIN S H, WANG Y, et al. Glutamic pyruvate transaminase GPT2 promotes tumorigenesis of breast cancer cells by activating sonic hedgehog signaling. Theranostics,2017,7(12): 3021–3033. doi: 10.7150/thno.18992
    [74] WU D D, YANG C P, WANG M S, et al. Convergent genomic signatures of high-altitude adaptation among domestic mammals. Nat Sci Rev,2019,7(6): 952–963. doi: 10.1093/molbev/msz158
    [75] YU L, WANG G D, RUAN J, et al. Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation. Nat Genet,2016,48(8): 947–952. doi: 10.1038/ng.3615
    [76] XU P, JIANG L, YANG Y, et al. PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation. Theranostics,2020,10(8): 3767–3778. doi: 10.7150/thno.43142
    [77] GORRINI C, HARRIS I S, MAK T W. Modulation of oxidative stress as an anticancer strategy. Nat Revi Drug Disc,2013,12(12): 931–947. doi: 10.1038/nrd4002
    [78] HUSSAIN T, TAN B, YIN Y, et al. Oxidative stress and inflammation: what polyphenols can do for us? Oxid Med Cell Longev, 2016, 2016:7432797[2029-12-03]. https://doi.org/10.1155/2016/7432797.
    [79] DOROSHOW J H. Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. Cancer Res,1983,43(10): 4543–4551.
    [80] MARCHETTI M, RESNICK L, GAMLIEL E, et al. Sulindac enhances the killing of cancer cells exposed to oxidative stress. PLoS One,2009,4(6): e5804[2020-12-15].https://doi.org/10.1371/journal.pone.0005804. doi: 10.1371/journal.pone.0005804
    [81] COLEMAN M C, ASBURY C R, DANIELS D, et al. 2-deoxy-D-glucose causes cytotoxicity, oxidative stress, and radiosensitization in pancreatic cancer. Free Radic Biol Med,2008,44(3): 322–331. doi: 10.1016/j.freeradbiomed.2007.08.032
    [82] PELICANO H, CARNEY D, HUANG P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat,2004,7(2): 97–110. doi: 10.1016/j.drup.2004.01.004
    [83] CHENG G, LANZA-JACOBY S. Metformin decreases growth of pancreatic cancer cells by decreasing reactive oxygen species: role of NOX4. Biochem Biophys Res Commun,2015,465(1): 41–46. doi: 10.1016/j.bbrc.2015.07.118
    [84] MOCHIZUKI T, FURUTA S, MITSUSHITA J, et al. Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Oncogene,2006,25(26): 3699–3707. doi: 10.1038/sj.onc.1209406
    [85] BRIEGER K, SCHIAVONE S, MILLER F J, JR, et al. Reactive oxygen species: from health to disease. Swiss Med Wkly,2012,142: w13659[2020-12-15].https://doi.org/10.4414/smw.2012.13659. doi: 10.4414/smw.2012.13659
  • 加载中
计量
  • 文章访问数:  677
  • HTML全文浏览量:  202
  • PDF下载量:  30
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-10-28
  • 修回日期:  2020-12-17
  • 刊出日期:  2021-01-20

目录

    /

    返回文章
    返回