IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39527-w.html
   My bibliography  Save this article

Cancer lineage-specific regulation of YAP responsive elements revealed through large-scale functional epigenomic screens

Author

Listed:
  • Inês A. M. Barbosa

    (Novartis Institutes for Biomedical Research)

  • Rajaraman Gopalakrishnan

    (Novartis Institutes for Biomedical Research
    Alltrna Inc., One Kendall Square)

  • Samuele Mercan

    (Novartis Institutes for Biomedical Research)

  • Thanos P. Mourikis

    (Novartis Institutes for Biomedical Research)

  • Typhaine Martin

    (Novartis Institutes for Biomedical Research)

  • Simon Wengert

    (Novartis Institutes for Biomedical Research
    Helmholtz Zentrum München GmbH German Research Center for Environmental Health)

  • Caibin Sheng

    (Novartis Institutes for Biomedical Research)

  • Fei Ji

    (Novartis Institutes for Biomedical Research)

  • Rui Lopes

    (Novartis Institutes for Biomedical Research
    Roche Pharmaceutical Research and Early Development)

  • Judith Knehr

    (Novartis Institutes for Biomedical Research)

  • Marc Altorfer

    (Novartis Institutes for Biomedical Research)

  • Alicia Lindeman

    (Novartis Institutes for Biomedical Research)

  • Carsten Russ

    (Novartis Institutes for Biomedical Research)

  • Ulrike Naumann

    (Novartis Institutes for Biomedical Research)

  • Javad Golji

    (Novartis Institutes for Biomedical Research)

  • Kathleen Sprouffske

    (Novartis Institutes for Biomedical Research)

  • Louise Barys

    (Novartis Institutes for Biomedical Research)

  • Luca Tordella

    (Novartis Institutes for Biomedical Research)

  • Dirk Schübeler

    (Friedrich Miescher Institute for Biomedical Research
    University of Basel)

  • Tobias Schmelzle

    (Novartis Institutes for Biomedical Research)

  • Giorgio G. Galli

    (Novartis Institutes for Biomedical Research)

Abstract

YAP is a key transcriptional co-activator of TEADs, it regulates cell growth and is frequently activated in cancer. In Malignant Pleural Mesothelioma (MPM), YAP is activated by loss-of-function mutations in upstream components of the Hippo pathway, while, in Uveal Melanoma (UM), YAP is activated in a Hippo-independent manner. To date, it is unclear if and how the different oncogenic lesions activating YAP impact its oncogenic program, which is particularly relevant for designing selective anti-cancer therapies. Here we show that, despite YAP being essential in both MPM and UM, its interaction with TEAD is unexpectedly dispensable in UM, limiting the applicability of TEAD inhibitors in this cancer type. Systematic functional interrogation of YAP regulatory elements in both cancer types reveals convergent regulation of broad oncogenic drivers in both MPM and UM, but also strikingly selective programs. Our work reveals unanticipated lineage-specific features of the YAP regulatory network that provide important insights to guide the design of tailored therapeutic strategies to inhibit YAP signaling across different cancer types.

Suggested Citation

  • Inês A. M. Barbosa & Rajaraman Gopalakrishnan & Samuele Mercan & Thanos P. Mourikis & Typhaine Martin & Simon Wengert & Caibin Sheng & Fei Ji & Rui Lopes & Judith Knehr & Marc Altorfer & Alicia Lindem, 2023. "Cancer lineage-specific regulation of YAP responsive elements revealed through large-scale functional epigenomic screens," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39527-w
    DOI: 10.1038/s41467-023-39527-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39527-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39527-w?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. Catherine D. Van Raamsdonk & Vladimir Bezrookove & Gary Green & Jürgen Bauer & Lona Gaugler & Joan M. O’Brien & Elizabeth M. Simpson & Gregory S. Barsh & Boris C. Bastian, 2009. "Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi," Nature, Nature, vol. 457(7229), pages 599-602, January.
    2. Matthew C. Canver & Elenoe C. Smith & Falak Sher & Luca Pinello & Neville E. Sanjana & Ophir Shalem & Diane D. Chen & Patrick G. Schupp & Divya S. Vinjamur & Sara P. Garcia & Sidinh Luc & Ryo Kurita &, 2015. "BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis," Nature, Nature, vol. 527(7577), pages 192-197, November.
    3. Drew T. Bergman & Thouis R. Jones & Vincent Liu & Judhajeet Ray & Evelyn Jagoda & Layla Siraj & Helen Y. Kang & Joseph Nasser & Michael Kane & Antonio Rios & Tung H. Nguyen & Sharon R. Grossman & Char, 2022. "Compatibility rules of human enhancer and promoter sequences," Nature, Nature, vol. 607(7917), pages 176-184, July.
    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. Patrick C Fiaux & Hsiuyi V Chen & Poshen B Chen & Aaron R Chen & Graham McVicker, 2020. "Discovering functional sequences with RELICS, an analysis method for CRISPR screens," PLOS Computational Biology, Public Library of Science, vol. 16(9), pages 1-23, September.
    2. Dongmei Wang & Haimin Li & Navdeep S. Chandel & Yali Dou & Rui Yi, 2023. "MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene promoters," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Yong-Seok Kim & Jun-Hee Yeon & Woori Ko & Byung-Chang Suh, 2023. "Two-step structural changes in M3 muscarinic receptor activation rely on the coupled Gq protein cycle," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Sandra Schrenk & Lindsay J. Bischoff & Jillian Goines & Yuqi Cai & Shruti Vemaraju & Yoshinobu Odaka & Samantha R. Good & Joseph S. Palumbo & Sara Szabo & Damien Reynaud & Catherine D. Raamsdonk & Ric, 2023. "MEK inhibition reduced vascular tumor growth and coagulopathy in a mouse model with hyperactive GNAQ," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Tomoyuki Ohno & Taichi Akase & Shunya Kono & Hikaru Kurasawa & Takuto Takashima & Shinya Kaneko & Yasunori Aizawa, 2022. "Biallelic and gene-wide genomic substitution for endogenous intron and retroelement mutagenesis in human cells," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Deborah E. Daniels & Ivan Ferrer-Vicens & Joseph Hawksworth & Tatyana N. Andrienko & Elizabeth M. Finnie & Natalie S. Bretherton & Daniel C. J. Ferguson & A. Sofia. F. Oliveira & Jenn-Yeu A. Szeto & M, 2023. "Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Jiaoyang Liao & Shuanghong Chen & Shenlin Hsiao & Yanhong Jiang & Yang Yang & Yuanjin Zhang & Xin Wang & Yongrong Lai & Daniel E. Bauer & Yuxuan Wu, 2023. "Therapeutic adenine base editing of human hematopoietic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. Colin McGaw & Anthony J. Garrity & Gabrielle Z. Munoz & Jeffrey R. Haswell & Sejuti Sengupta & Elise Keston-Smith & Pratyusha Hunnewell & Alexa Ornstein & Mishti Bose & Quinton Wessells & Noah Jakimo , 2022. "Engineered Cas12i2 is a versatile high-efficiency platform for therapeutic genome editing," Nature Communications, Nature, vol. 13(1), pages 1-11, 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:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39527-w. 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: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    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.