IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28801-y.html
   My bibliography  Save this article

Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma

Author

Listed:
  • Claudia Capparelli

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Timothy J. Purwin

    (Thomas Jefferson University)

  • McKenna Glasheen

    (Thomas Jefferson University)

  • Signe Caksa

    (Thomas Jefferson University)

  • Manoela Tiago

    (Thomas Jefferson University)

  • Nicole Wilski

    (Thomas Jefferson University)

  • Danielle Pomante

    (Thomas Jefferson University)

  • Sheera Rosenbaum

    (Thomas Jefferson University)

  • Mai Q. Nguyen

    (Thomas Jefferson University)

  • Weijia Cai

    (Thomas Jefferson University)

  • Janusz Franco-Barraza

    (Fox Chase Cancer Center)

  • Richard Zheng

    (Thomas Jefferson University)

  • Gaurav Kumar

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Inna Chervoneva

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Ayako Shimada

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Vito W. Rebecca

    (The Wistar Institute
    Johns Hopkins University Bloomberg School of Public Health)

  • Adam E. Snook

    (Thomas Jefferson University
    Thomas Jefferson University)

  • Kim Hookim

    (Thomas Jefferson University)

  • Xiaowei Xu

    (Perelman School of Medicine, University of Pennsylvania)

  • Edna Cukierman

    (Fox Chase Cancer Center)

  • Meenhard Herlyn

    (The Wistar Institute)

  • Andrew E. Aplin

    (Thomas Jefferson University
    Thomas Jefferson University)

Abstract

Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells.

Suggested Citation

  • Claudia Capparelli & Timothy J. Purwin & McKenna Glasheen & Signe Caksa & Manoela Tiago & Nicole Wilski & Danielle Pomante & Sheera Rosenbaum & Mai Q. Nguyen & Weijia Cai & Janusz Franco-Barraza & Ric, 2022. "Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28801-y
    DOI: 10.1038/s41467-022-28801-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28801-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28801-y?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. Sydney M. Shaffer & Margaret C. Dunagin & Stefan R. Torborg & Eduardo A. Torre & Benjamin Emert & Clemens Krepler & Marilda Beqiri & Katrin Sproesser & Patricia A. Brafford & Min Xiao & Elliott Eggan , 2017. "Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance," Nature, Nature, vol. 546(7658), pages 431-435, June.
    2. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
    3. Shujun Han & Yibo Ren & Wangxiao He & Huadong Liu & Zhe Zhi & Xinliang Zhu & Tielin Yang & Yu Rong & Bohan Ma & Timothy J. Purwin & Zhenlin Ouyang & Caixia Li & Xun Wang & Xueqiang Wang & Huizi Yang &, 2018. "ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    4. Eleonora Leucci & Roberto Vendramin & Marco Spinazzi & Patrick Laurette & Mark Fiers & Jasper Wouters & Enrico Radaelli & Sven Eyckerman & Carina Leonelli & Katrien Vanderheyden & Aljosja Rogiers & El, 2016. "Melanoma addiction to the long non-coding RNA SAMMSON," Nature, Nature, vol. 531(7595), pages 518-522, March.
    5. Meghna Das Thakur & Fernando Salangsang & Allison S. Landman & William R. Sellers & Nancy K. Pryer & Mitchell P. Levesque & Reinhard Dummer & Martin McMahon & Darrin D. Stuart, 2013. "Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance," Nature, Nature, vol. 494(7436), pages 251-255, February.
    6. Judith Müller & Oscar Krijgsman & Jennifer Tsoi & Lidia Robert & Willy Hugo & Chunying Song & Xiangju Kong & Patricia A. Possik & Paulien D. M. Cornelissen-Steijger & Marnix H Geukes Foppen & Kristel , 2014. "Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    7. Annelien Verfaillie & Hana Imrichova & Zeynep Kalender Atak & Michael Dewaele & Florian Rambow & Gert Hulselmans & Valerie Christiaens & Dmitry Svetlichnyy & Flavie Luciani & Laura Van den Mooter & So, 2015. "Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state," Nature Communications, Nature, vol. 6(1), pages 1-16, May.
    8. Chong Sun & Liqin Wang & Sidong Huang & Guus J. J. E. Heynen & Anirudh Prahallad & Caroline Robert & John Haanen & Christian Blank & Jelle Wesseling & Stefan M. Willems & Davide Zecchin & Sebastijan H, 2014. "Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma," Nature, Nature, vol. 508(7494), pages 118-122, April.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Guillaume Harmange & Raúl A. Reyes Hueros & Dylan L. Schaff & Benjamin Emert & Michael Saint-Antoine & Laura C. Kim & Zijian Niu & Shivani Nellore & Mitchell E. Fane & Gretchen M. Alicea & Ashani T. W, 2023. "Disrupting cellular memory to overcome drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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. Guillaume Harmange & Raúl A. Reyes Hueros & Dylan L. Schaff & Benjamin Emert & Michael Saint-Antoine & Laura C. Kim & Zijian Niu & Shivani Nellore & Mitchell E. Fane & Gretchen M. Alicea & Ashani T. W, 2023. "Disrupting cellular memory to overcome drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Anastasia Samarkina & Markus Kirolos Youssef & Paola Ostano & Soumitra Ghosh & Min Ma & Beatrice Tassone & Tatiana Proust & Giovanna Chiorino & Mitchell P. Levesque & Sandro Goruppi & Gian Paolo Dotto, 2023. "Androgen receptor is a determinant of melanoma targeted drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Miles C. Andrews & Junna Oba & Chang-Jiun Wu & Haifeng Zhu & Tatiana Karpinets & Caitlin A. Creasy & Marie-Andrée Forget & Xiaoxing Yu & Xingzhi Song & Xizeng Mao & A. Gordon Robertson & Gabriele Roma, 2022. "Multi-modal molecular programs regulate melanoma cell state," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Ruitong Li & Olaf Klingbeil & Davide Monducci & Michael J. Young & Diego J. Rodriguez & Zaid Bayyat & Joshua M. Dempster & Devishi Kesar & Xiaoping Yang & Mahdi Zamanighomi & Christopher R. Vakoc & Ta, 2022. "Comparative optimization of combinatorial CRISPR screens," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Michael F. Emmons & Richard L. Bennett & Alberto Riva & Kanchan Gupta & Larissa Anastasio Da Costa Carvalho & Chao Zhang & Robert Macaulay & Daphne Dupéré-Richér & Bin Fang & Edward Seto & John M. Koo, 2023. "HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Caitlin E. Mills & Kartik Subramanian & Marc Hafner & Mario Niepel & Luca Gerosa & Mirra Chung & Chiara Victor & Benjamin Gaudio & Clarence Yapp & Ajit J. Nirmal & Nicholas Clark & Peter K. Sorger, 2022. "Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    7. Dianne Lumaquin-Yin & Emily Montal & Eleanor Johns & Arianna Baggiolini & Ting-Hsiang Huang & Yilun Ma & Charlotte LaPlante & Shruthy Suresh & Lorenz Studer & Richard M. White, 2023. "Lipid droplets are a metabolic vulnerability in melanoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Nadege Gitego & Bogos Agianian & Oi Wei Mak & Vasantha Kumar MV & Emily H. Cheng & Evripidis Gavathiotis, 2023. "Chemical modulation of cytosolic BAX homodimer potentiates BAX activation and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    9. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Franziska Haderk & Yu-Ting Chou & Lauren Cech & Celia Fernández-Méndez & Johnny Yu & Victor Olivas & Ismail M. Meraz & Dora Barbosa Rabago & D. Lucas Kerr & Carlos Gomez & David V. Allegakoen & Juan G, 2024. "Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Singh, Abhyudai & Vahdat, Zahra & Xu, Zikai, 2019. "Time-triggered stochastic hybrid systems with two timer-dependent resets," OSF Preprints u8fzg, Center for Open Science.
    13. Xue Zhang & Shishir M. Pant & Cecily C. Ritch & Hsin-Yao Tang & Hongguang Shao & Harsh Dweep & Yao-Yu Gong & Rebekah Brooks & Patricia Brafford & Adam J. Wolpaw & Yool Lee & Ashani Weeraratna & Amita , 2024. "Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    14. Fei Li & Yizhe Wang & Inah Hwang & Ja-Young Jang & Libo Xu & Zhong Deng & Eun Young Yu & Yiming Cai & Caizhi Wu & Zhenbo Han & Yu-Han Huang & Xiangao Huang & Ling Zhang & Jun Yao & Neal F. Lue & Paul , 2023. "Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    16. Pakavarin Louphrasitthiphol & Alessia Loffreda & Vivian Pogenberg & Sarah Picaud & Alexander Schepsky & Hans Friedrichsen & Zhiqiang Zeng & Anahita Lashgari & Benjamin Thomas & E. Elizabeth Patton & M, 2023. "Acetylation reprograms MITF target selectivity and residence time," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    17. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    18. Heike Chauvistré & Batool Shannan & Sheena M. Daignault-Mill & Robert J. Ju & Daniel Picard & Stefanie Egetemaier & Renáta Váraljai & Christine S. Gibhardt & Antonio Sechi & Farnusch Kaschani & Oliver, 2022. "Persister state-directed transitioning and vulnerability in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    19. Roberta Esposito & Andrés Lanzós & Tina Uroda & Sunandini Ramnarayanan & Isabel Büchi & Taisia Polidori & Hugo Guillen-Ramirez & Ante Mihaljevic & Bernard Mefi Merlin & Lia Mela & Eugenio Zoni & Lusin, 2023. "Tumour mutations in long noncoding RNAs enhance cell fitness," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    20. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:13:y:2022:i:1:d:10.1038_s41467-022-28801-y. 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.