RGD Reference Report - PHOX2B is a suppressor of neuroblastoma metastasis. - Rat Genome Database

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PHOX2B is a suppressor of neuroblastoma metastasis.

Authors: Naftali, Osnat  Maman, Shelly  Meshel, Tsipi  Sagi-Assif, Orit  Ginat, Ravit  Witz, Isaac P 
Citation: Naftali O, etal., Oncotarget. 2016 Mar 1;7(9):10627-37. doi: 10.18632/oncotarget.7056.
RGD ID: 151667442
Pubmed: PMID:26840262   (View Abstract at PubMed)
PMCID: PMC4891146   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.7056   (Journal Full-text)

Paired like homeobox 2B (PHOX2B) is a minimal residual disease (MRD) marker of neuroblastoma. The presence of MRD, also referred to as micro-metastases, is a powerful marker of poor prognosis in neuroblastoma. Lung metastasis is considered a terminal event in neuroblastoma. Lung micro-metastatic neuroblastoma (MicroNB) cells show high expression levels of PHOX2B and possess a less malignant and metastatic phenotype than lung macro metastatic neuroblastoma (MacroNB) cells, which hardly express PHOX2B. In vitro assays showed that PHOX2B knockdown in MicroNB cells did not affect cell viability; however it decreased the migratory capacity of the MicroNB-shPHOX2B cells. An orthotopic inoculation of MicroNB-shPHOX2B cells into the adrenal gland of nude mice resulted in significantly larger primary tumors and a heavier micro-metastatic load in the lungs and bone-marrow, than when control cells were inoculated. PHOX2B expression was found to be regulated by methylation. The PHOX2B promoter in MacroNB cells is significantly more methylated than in MicroNB cells. Demethylation assays using 5-azacytidine demonstrated that methylation can indeed inhibit PHOX2B transcription in MacroNB cells. These pre-clinical data strongly suggest that PHOX2B functions as a suppressor of neuroblastoma progression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuroblastoma exacerbatesIMP 151667442human cell line in a mouse modelRGD 
neuroblastoma exacerbatesISOPHOX2B (Homo sapiens)151667442; 151667442human cell line in a mouse modelRGD 

Objects Annotated

Genes (Rattus norvegicus)
Phox2b  (paired-like homeobox 2b)

Genes (Mus musculus)
Phox2b  (paired-like homeobox 2b)

Genes (Homo sapiens)
PHOX2B  (paired like homeobox 2B)


Additional Information