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Identification of the tumour transition states occurring during EMT

Author

Listed:
  • Ievgenia Pastushenko

    (Université Libre de Buxelles)

  • Audrey Brisebarre

    (Université Libre de Buxelles)

  • Alejandro Sifrim

    (University of Leuven
    Wellcome Trust Sanger Institute)

  • Marco Fioramonti

    (Université Libre de Buxelles)

  • Tatiana Revenco

    (Université Libre de Buxelles)

  • Soufiane Boumahdi

    (Université Libre de Buxelles)

  • Alexandra Van Keymeulen

    (Université Libre de Buxelles)

  • Daniel Brown

    (University of Leuven
    VIB Center for Cancer Biology)

  • Virginie Moers

    (Université Libre de Buxelles)

  • Sophie Lemaire

    (Université Libre de Buxelles)

  • Sarah De Clercq

    (Université Libre de Bruxelles)

  • Esmeralda Minguijón

    (Université Libre de Bruxelles)

  • Cédric Balsat

    (Université Libre de Bruxelles)

  • Youri Sokolow

    (Université Libre de Bruxelles)

  • Christine Dubois

    (Université Libre de Buxelles)

  • Florian De Cock

    (Université Libre de Buxelles)

  • Samuel Scozzaro

    (Université Libre de Buxelles)

  • Federico Sopena

    (Hospital Clínico Universitario “Lozano Blesa”, IIS Aragon)

  • Angel Lanas

    (University of Zaragoza)

  • Nicky D’Haene

    (Université Libre de Bruxelles)

  • Isabelle Salmon

    (Université Libre de Bruxelles)

  • Jean-Christophe Marine

    (VIB Center for Cancer Biology
    KU Leuven)

  • Thierry Voet

    (University of Leuven
    Wellcome Trust Sanger Institute)

  • Panagiota A. Sotiropoulou

    (Université Libre de Buxelles)

  • Cédric Blanpain

    (Université Libre de Buxelles
    WELBIO, Université Libre de Bruxelles)

Abstract

In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.

Suggested Citation

  • Ievgenia Pastushenko & Audrey Brisebarre & Alejandro Sifrim & Marco Fioramonti & Tatiana Revenco & Soufiane Boumahdi & Alexandra Van Keymeulen & Daniel Brown & Virginie Moers & Sophie Lemaire & Sarah , 2018. "Identification of the tumour transition states occurring during EMT," Nature, Nature, vol. 556(7702), pages 463-468, April.
    • Handle: RePEc:nat:nature:v:556:y:2018:i:7702:d:10.1038_s41586-018-0040-3
    DOI: 10.1038/s41586-018-0040-3
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    Cited by:

    1. Patrick Aouad & Yueyun Zhang & Fabio Martino & Céline Stibolt & Simak Ali & Giovanna Ambrosini & Sendurai A. Mani & Kelly Maggs & Hazel M. Quinn & George Sflomos & Cathrin Brisken, 2022. "Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Yael Aylon & Noa Furth & Giuseppe Mallel & Gilgi Friedlander & Nishanth Belugali Nataraj & Meng Dong & Ori Hassin & Rawan Zoabi & Benjamin Cohen & Vanessa Drendel & Tomer Meir Salame & Saptaparna Mukh, 2022. "Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive axis," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Nastaran Mohammadi Ghahhari & Magdalena K. Sznurkowska & Nicolas Hulo & Lilia Bernasconi & Nicola Aceto & Didier Picard, 2022. "Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Guidantonio Malagoli Tagliazucchi & Anna J. Wiecek & Eloise Withnell & Maria Secrier, 2023. "Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Cécile Thirant & Agathe Peltier & Simon Durand & Amira Kramdi & Caroline Louis-Brennetot & Cécile Pierre-Eugène & Margot Gautier & Ana Costa & Amandine Grelier & Sakina Zaïdi & Nadège Gruel & Irène Ji, 2023. "Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Laura Lorenzo-Sanz & Marta Lopez-Cerda & Victoria da Silva-Diz & Marta H. Artés & Sandra Llop & Rosa M. Penin & Josep Oriol Bermejo & Eva Gonzalez-Suarez & Manel Esteller & Francesc Viñals & Enrique E, 2024. "Cancer cell plasticity defines response to immunotherapy in cutaneous squamous cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. Peter Bailey & Rachel A. Ridgway & Patrizia Cammareri & Mairi Treanor-Taylor & Ulla-Maja Bailey & Christina Schoenherr & Max Bone & Daniel Schreyer & Karin Purdie & Jason Thomson & William Rickaby & R, 2023. "Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Mrinmoy Mukherjee & Herbert Levine, 2021. "Cluster size distribution of cells disseminating from a primary tumor," PLOS Computational Biology, Public Library of Science, vol. 17(11), pages 1-23, November.
    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. Steffen Plunder & Cathy Danesin & Bruno Glise & Marina A. Ferreira & Sara Merino-Aceituno & Eric Theveneau, 2024. "Modelling variability and heterogeneity of EMT scenarios highlights nuclear positioning and protrusions as main drivers of extrusion," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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