PreprintCited by 16Neuroblastoma Research and TreatmentsNeurofibromatosis and Schwannoma CasesDevelopmental Biology and Gene Regulation

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TWIST1 expression is associated with high-risk Neuroblastoma and promotes Primary and Metastatic Tumor Growth

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Sepporta, Maria-Vittoria, Praz, Viviane, Bourloud, Katia Balmas, Joseph, Jean-Marc, Jauquier, Nicolas, Riggi, Nicolo’, Nardou-Auderset, Katya, Petit, Audrey, Scoazec, Jean-Yves, Sartelet, Hervé, Renella, Raffaele, Mühlethaler-Mottet, Annick·2021·Communications Biology

Preprint — published as 10.1038/s42003-021-02958-6 · Paper page

Abstract

The embryonic transcription factors TWIST1/2 are frequently overexpressed in cancer, acting as multifunctional oncogenes. Here we investigate their role in neuroblastoma (NB), a heterogeneous childhood malignancy ranging from spontaneous regression to dismal outcomes despite multimodal therapy. We first reveal the association of TWIST1 expression with poor survival and metastasis in primary NB, while TWIST2 correlates with good prognosis. Secondly, suppression of TWIST1 by CRISPR/Cas9 results in a reduction of tumor growth and metastasis colonization in immunocompromised mice. Moreover, TWIST1 knockout tumors display a less aggressive cellular morphology and a reduced disruption of the extracellular matrix (ECM) reticulin network. Additionally, we identify a TWIST1-mediated transcriptional program associated with dismal outcome in NB and involved in the control of pathways mainly linked to the signaling, migration, adhesion, the organization of the ECM, and the tumor cells versus tumor stroma crosstalk. Taken together, our findings suggest TWIST1 as novel therapeutic target in NB.

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Metadata

Authors
Sepporta, M.-V., Praz, V., Bourloud, K. B., Joseph, J.-M., Jauquier, N., Riggi, N., Nardou-Auderset, K., Petit, A., Scoazec, J.-Y., Sartelet, H., Renella, R., & Mühlethaler-Mottet, A.
Affiliations
  • Centre Hospitalier Universitaire Vaudois (CH)
  • Hôpital de la Timone (FR)
  • Institut Gustave Roussy (FR)
  • Centre Hospitalier Régional et Universitaire de Nancy (FR)
Venue
Communications Biology
Publisher
openRxiv
Published
2021-03-22
Volume
5
Issue
1
Pages
42-42
ISSN
2399-3642 (ISSN-L)
OpenAlex
W4220760725
Cited by
16
References
1
Citations by year
2026: 6 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 1
FWCI
1.32
Type
journal article
Language
en
Open access
Locations
  • Communications Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, cc-by)
  • IRIS (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
Funders
  • Novartis Foundation
  • École Polytechnique Fédérale de Lausanne
  • Novartis Stiftung für Medizinisch-Biologische Forschung
  • Université de Lausanne
Topics
  • Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
  • Health Sciences › Medicine › Clinical Neurology › Neurofibromatosis and Schwannoma Cases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
TWIST1, TWIST2, neuroblastoma, high-risk neuroblastoma, metastasis, tumor growth, embryonic transcription factors, oncogenes, prognosis, survival, extracellular matrix, tumor-stroma interactions, cell adhesion and migration, therapeutic target, CRISPR/Cas9 knockout
MeSH terms
Animals, Neuroblastoma, Nuclear Proteins, Gene Expression, Gene Expression Regulation, Neoplastic, Immunocompromised Host, Mice, Twist-Related Protein 1

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