GAS7 Deficiency Promotes Metastasis in MYCN-driven Neuroblastoma
- Dong, Z., Yeo, K.S., Lopez, G., Zhang, C., Dankert Eggum, E.N., Rokita, J.L., Ung, C.Y., Levee, T.M., Her, Z.P., Howe, C.J., Hou, X., van Ree, J.H., Li, S., He, S., Tao, T., Fritchie, K., Torres-Mora, J., Lehman, J.S., Meves, A., Razidlo, G.L., Rathi, K.S., Weroha, S.J., Look, A.T., van Deursen, J.M., Li, H., Westendorf, J.J., Maris, J.M., Zhu, S.
- Cancer research 81(11): 2995-3007 (Journal)
- Registered Authors
- Dong, Zhiwei, Zhu, Shizhen
- MeSH Terms
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism*
- Bone Marrow Neoplasms/genetics
- Bone Marrow Neoplasms/metabolism
- Bone Marrow Neoplasms/secondary*
- Cell Proliferation
- Chromosome Deletion*
- Gene Expression Regulation, Neoplastic*
- Mice, SCID
- N-Myc Proto-Oncogene Protein/genetics
- N-Myc Proto-Oncogene Protein/metabolism*
- Nerve Tissue Proteins/deficiency*
- Nerve Tissue Proteins/genetics
- Survival Rate
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
- 33602789 Full text @ Cancer Res.
Dong, Z., Yeo, K.S., Lopez, G., Zhang, C., Dankert Eggum, E.N., Rokita, J.L., Ung, C.Y., Levee, T.M., Her, Z.P., Howe, C.J., Hou, X., van Ree, J.H., Li, S., He, S., Tao, T., Fritchie, K., Torres-Mora, J., Lehman, J.S., Meves, A., Razidlo, G.L., Rathi, K.S., Weroha, S.J., Look, A.T., van Deursen, J.M., Li, H., Westendorf, J.J., Maris, J.M., Zhu, S. (2021) GAS7 Deficiency Promotes Metastasis in MYCN-driven Neuroblastoma. Cancer research. 81(11):2995-3007.
One of the greatest barriers to curative treatment of neuroblastoma (NB) is its frequent metastatic outgrowth prior to diagnosis, especially in cases driven by amplification of the MYCN oncogene. However, only a limited number of regulatory proteins that contribute to this complex MYCN-mediated process have been elucidated. Here we show that the growth arrest-specific 7 (GAS7) gene, located at chromosome band 17p13.1, is preferentially deleted in high-risk MYCN-driven NB. GAS7 expression was also suppressed in MYCN-amplified NB lacking 17p deletion. GAS7 deficiency led to accelerated metastasis in both zebrafish and mammalian models of NB with overexpression or amplification of MYCN. Analysis of expression profiles and the ultrastructure of zebrafish NB tumors with MYCN overexpression identified that GAS7 deficiency led to (i) downregulation of genes involved in cell-cell interaction, (ii) loss of contact among tumor cells as critical determinants of accelerated metastasis, and (iii) increased levels of MYCN protein. These results provide the first genetic evidence that GAS7 depletion is a critical early step in the cascade of events culminating in NB metastasis in the context of MYCN overexpression.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes