IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0134645.html
   My bibliography  Save this article

Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer

Author

Listed:
  • Rafik Salama
  • Norma Masson
  • Peter Simpson
  • Lina Katrin Sciesielski
  • Min Sun
  • Ya-Min Tian
  • Peter John Ratcliffe
  • David Robert Mole

Abstract

General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.

Suggested Citation

  • Rafik Salama & Norma Masson & Peter Simpson & Lina Katrin Sciesielski & Min Sun & Ya-Min Tian & Peter John Ratcliffe & David Robert Mole, 2015. "Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-19, August.
    • Handle: RePEc:plo:pone00:0134645
    DOI: 10.1371/journal.pone.0134645
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134645
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0134645&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0134645?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Caryn S. Ross-Innes & Rory Stark & Andrew E. Teschendorff & Kelly A. Holmes & H. Raza Ali & Mark J. Dunning & Gordon D. Brown & Ondrej Gojis & Ian O. Ellis & Andrew R. Green & Simak Ali & Suet-Feung C, 2012. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer," Nature, Nature, vol. 481(7381), pages 389-393, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yawen Lei & Yaoguang Yu & Wei Fu & Tao Zhu & Caihong Wu & Zhihao Zhang & Zewang Yu & Xin Song & Jianqu Xu & Zhenwei Liang & Peitao Lü & Chenlong Li, 2024. "BCL7A and BCL7B potentiate SWI/SNF-complex-mediated chromatin accessibility to regulate gene expression and vegetative phase transition in plants," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Yanjiang Liu & Gongcheng Hu & Shengxiong Yang & Mingze Yao & Zicong Liu & Chenghong Yan & Yulin Wen & Wangfang Ping & Juehan Wang & Yawei Song & Xiaotao Dong & Guangjin Pan & Hongjie Yao, 2023. "Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Andreas Lackner & Michael Müller & Magdalena Gamperl & Delyana Stoeva & Olivia Langmann & Henrieta Papuchova & Elisabeth Roitinger & Gerhard Dürnberger & Richard Imre & Karl Mechtler & Paulina A. Lato, 2023. "The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Congcong Tian & Jiaqi Zhou & Xinran Li & Yuan Gao & Qing Wen & Xing Kang & Nan Wang & Yuan Yao & Jiuhang Jiang & Guibing Song & Tianjun Zhang & Suili Hu & JingYi Liao & Chuanhe Yu & Zhiquan Wang & Xia, 2023. "Impaired histone inheritance promotes tumor progression," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Haoxi Chai & Harianto Tjong & Peng Li & Wei Liao & Ping Wang & Chee Hong Wong & Chew Yee Ngan & Warren J. Leonard & Chia-Lin Wei & Yijun Ruan, 2023. "ChIATAC is an efficient strategy for multi-omics mapping of 3D epigenomes from low-cell inputs," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Tulsi Patel & Jennifer Hammelman & Siaresh Aziz & Sumin Jang & Michael Closser & Theodore L. Michaels & Jacob A. Blum & David K. Gifford & Hynek Wichterle, 2022. "Transcriptional dynamics of murine motor neuron maturation in vivo and in vitro," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    7. Sayantani Ghosh Dastidar & Bony Kumar & Bo Lauckner & Damien Parrello & Danielle Perley & Maria Vlasenok & Antariksh Tyagi & Nii Koney-Kwaku Koney & Ata Abbas & Sergei Nechaev, 2023. "Transcriptional responses of cancer cells to heat shock-inducing stimuli involve amplification of robust HSF1 binding," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Hiroko Nomaru & Yang Liu & Christopher De Bono & Dario Righelli & Andrea Cirino & Wei Wang & Hansoo Song & Silvia E. Racedo & Anelisa G. Dantas & Lu Zhang & Chen-Leng Cai & Claudia Angelini & Lionel C, 2021. "Single cell multi-omic analysis identifies a Tbx1-dependent multilineage primed population in murine cardiopharyngeal mesoderm," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    9. Qiutao Xu & Yaping Yue & Biao Liu & Zhengting Chen & Xuan Ma & Jing Wang & Yu Zhao & Dao-Xiu Zhou, 2023. "ACL and HAT1 form a nuclear module to acetylate histone H4K5 and promote cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Jamal B. Williams & Qing Cao & Wei Wang & Young-Ho Lee & Luye Qin & Ping Zhong & Yong Ren & Kaijie Ma & Zhen Yan, 2023. "Inhibition of histone methyltransferase Smyd3 rescues NMDAR and cognitive deficits in a tauopathy mouse model," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. Konstantin Okonechnikov & Aylin Camgöz & Owen Chapman & Sameena Wani & Donglim Esther Park & Jens-Martin Hübner & Abhijit Chakraborty & Meghana Pagadala & Rosalind Bump & Sahaana Chandran & Katerina K, 2023. "3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    13. Siqian Feng & Chaitanya Rastogi & Ryan Loker & William J. Glassford & H. Tomas Rube & Harmen J. Bussemaker & Richard S. Mann, 2022. "Transcription factor paralogs orchestrate alternative gene regulatory networks by context-dependent cooperation with multiple cofactors," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    14. Jing Chen & Zhen Hu & Mukta Phatak & John Reichard & Johannes M Freudenberg & Siva Sivaganesan & Mario Medvedovic, 2013. "Genome-Wide Signatures of Transcription Factor Activity: Connecting Transcription Factors, Disease, and Small Molecules," PLOS Computational Biology, Public Library of Science, vol. 9(9), pages 1-12, September.
    15. Kadir Buyukcelebi & Xintong Chen & Fatih Abdula & Hoda Elkafas & Alexander James Duval & Harun Ozturk & Fidan Seker-Polat & Qiushi Jin & Ping Yin & Yue Feng & Serdar E. Bulun & Jian Jun Wei & Feng Yue, 2023. "Engineered MED12 mutations drive leiomyoma-like transcriptional and metabolic programs by altering the 3D genome compartmentalization," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Joyce J. Thompson & Daniel J. Lee & Apratim Mitra & Sarah Frail & Ryan K. Dale & Pedro P. Rocha, 2022. "Extensive co-binding and rapid redistribution of NANOG and GATA6 during emergence of divergent lineages," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Junhao Li & Manoj K. Jaiswal & Jo-Fan Chien & Alexey Kozlenkov & Jinyoung Jung & Ping Zhou & Mahammad Gardashli & Luc J. Pregent & Erica Engelberg-Cook & Dennis W. Dickson & Veronique V. Belzil & Eran, 2023. "Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    18. Paola Cattaneo & Michael G. B. Hayes & Nina Baumgarten & Dennis Hecker & Sofia Peruzzo & Galip S. Aslan & Paolo Kunderfranco & Veronica Larcher & Lunfeng Zhang & Riccardo Contu & Gregory Fonseca & Sim, 2022. "DOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    19. Eudald Pascual-Carreras & Marta Marín-Barba & Sergio Castillo-Lara & Pablo Coronel-Córdoba & Marta Silvia Magri & Grant N. Wheeler & Jose Luis Gómez-Skarmeta & Josep F. Abril & Emili Saló & Teresa Ade, 2023. "Wnt/β-catenin signalling is required for pole-specific chromatin remodeling during planarian regeneration," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Joschka Hey & Michelle Paulsen & Reka Toth & Dieter Weichenhan & Simone Butz & Jolanthe Schatterny & Reinhard Liebers & Pavlo Lutsik & Christoph Plass & Marcus A. Mall, 2021. "Epigenetic reprogramming of airway macrophages promotes polarization and inflammation in muco-obstructive lung disease," Nature Communications, Nature, vol. 12(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0134645. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.