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

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License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_0BD66261314E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TWIST1 expression is associated with high-risk Neuroblastoma and promotes Primary and Metastatic Tumor Growth
Journal
BioRxiv
Author(s)
Sepporta MV, Praz V., Balmas Bourloud K., Joseph JM, Jauquier N., Riggi N., Nardou-Auderset K., Petit A., Scoazec JY, Sartelet H., Renella R., Muhlethaler-Mottet A.
Publication state
Published
Issued date
22/03/2021
Language
english
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 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.
Open Access
Yes
Create date
23/03/2021 21:28
Last modification date
08/04/2021 7:08
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