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

Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE

Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]-

Gene Expression* ; Gene Expression Regulation, Neoplastic* ; Neuroblastoma*/pathology ; Neuroblastoma*/secondary; Nuclear Proteins/*genetics ; Twist-Related Protein 1/*genetics; Animals ; Immunocompromised Host ; Mice ; Nuclear Proteins/metabolism ; Twist-Related Protein 1/metabolism

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.
(© 2022. The Author(s).)

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0 (Nuclear Proteins)
0 (TWIST1 protein, human)
0 (Twist-Related Protein 1)

Date Created: 20220113 Date Completed: 20220303 Latest Revision: 20240405

20240405

PMC8755726

10.1038/s42003-021-02958-6

35022561