TWIST1 expression is associated with high-risk neuroblastoma and promotes primary and metastatic tumor growth.

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.

• Authors: Maria-Vittoria Sepporta, Viviane Praz, Katia Balmas Bourloud, Jean-Marc Joseph, Nicolas Jauquier, Nicolò Riggi, Katya Nardou-Auderset, Audrey Petit, Jean-Yves Scoazec, Hervé Sartelet, Raffaele Renella, Annick Mühlethaler-Mottet
• Journal: Communications biology (Commun Biol) Vol. 5 Issue 1 Pg. 42 (01 12 2022) ISSN: 2399-3642 [Electronic] England
• PMID: 35022561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Nuclear Proteins
• TWIST1 protein, human
• Twist-Related Protein 1

Topics

• Animals
• Gene Expression
• Gene Expression Regulation, Neoplastic
• Immunocompromised Host
• Mice
• Neuroblastoma (pathology, secondary)
• Nuclear Proteins (genetics, metabolism)
• Twist-Related Protein 1 (genetics, metabolism)