TWIST1 expression is associated with high-risk neuroblastoma and promotes primary and metastatic tumor growth
Open accessPublished version of a preprint
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 confirm TWIST1 as promising therapeutic target in NB.
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Cites
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- Authors
- Sepporta, M.-V., Praz, V., Balmas Bourloud, K., 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)
- ORCID
- Venue
- Communications Biology
- Published
- 2022-01-12
- Volume
- 5
- Issue
- 1
- Pages
- 42-42
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC8755726
- OpenAlex
- W4220760725
- Cited by
- 16
- References
- 4
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 1
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- 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
- Force foundation
- Novartis Stiftung für Medizinisch-Biologische Forschung
- Stiftung Kinderkrebsforschung Schweiz (Switzerland) FORCE foundation (Switzerland) Hubert Gouin Association
- Topics
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Health Sciences › Medicine › 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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