CHD5 inhibits metastasis of neuroblastoma

CHD5 , a tumor suppressor at 1p36, is frequently lost or silenced in poor prognosis neuroblastoma (NB) and many adult cancers. The role of CHD5 in metastasis is unknown. We confirm that low expression of CHD5 is associated with stage 4 NB. Forced expression of CHD5 in NB cell lines with 1p loss inhi...

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Bibliographic Details
Published in:Oncogene 2022-01, Vol.41 (5), p.622-633
Main Authors: Laut, Astrid K., Dorneburg, Carmen, Fürstberger, Axel, Barth, Thomas F. E., Kestler, Hans A., Debatin, Klaus-Michael, Beltinger, Christian
Format: Article
Language:English
Subjects:
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Animals
Apoptosis
Bone growth
Bone marrow
Cell Biology
Cell Line, Tumor
Cell Movement - genetics
DNA Helicases - genetics
DNA Helicases - metabolism
Gene expression
Gene Expression Regulation, Neoplastic
Genomes
Human Genetics
Humans
Internal Medicine
Medical prognosis
Medicine
Medicine & Public Health
Metastases
Metastasis
Mice
mRNA
Neoplasm Invasiveness - genetics
Neoplasm Metastasis
Nerve Tissue Proteins
Neuroblastoma
Neuroblastoma - genetics
Neuroblastoma - metabolism
Neuroblastoma - pathology
Oncology
p53 Protein
Tumor suppressor genes
Tumors
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Summary:CHD5 , a tumor suppressor at 1p36, is frequently lost or silenced in poor prognosis neuroblastoma (NB) and many adult cancers. The role of CHD5 in metastasis is unknown. We confirm that low expression of CHD5 is associated with stage 4 NB. Forced expression of CHD5 in NB cell lines with 1p loss inhibited key aspects of the metastatic cascade in vitro: anchorage-independent growth, migration, and invasion. In vivo, formation of bone marrow and liver metastases developing from intravenously injected NB cells was delayed and decreased by forced CHD5 expression. Genome-wide mRNA sequencing revealed reduction of genes and gene sets associated with metastasis when CHD5 was overexpressed. Known metastasis-suppressing genes preferentially upregulated in CHD5-overexpressing NB cells included PLCL1 . In patient NB, low expression of PLCL1was associated with metastatic disease and poor survival. Knockdown of PLCL1 and of p53 in IMR5 NB cells overexpressing CHD5 reversed CHD5-induced inhibition of invasion and migration in vitro. In summary, CHD5 is a metastasis suppressor in NB.
ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-021-02081-0