@article{a5ceae14ec5c435b92bd22378fb9a6ec,
title = "GAS7 deficiency promotes metastasis in MYCN-driven neuroblastoma",
abstract = "One of the greatest barriers to curative treatment of neuroblastoma 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 neuroblastoma. GAS7 expression was also suppressed in MYCN-amplified neuroblastoma lacking 17p deletion. GAS7 deficiency led to accelerated metastasis in both zebrafish and mammalian models of neuroblastoma with overexpression or amplification of MYCN. Analysis of expression profiles and the ultrastructure of zebrafish neuroblastoma 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 neuroblastoma metastasis in the context of MYCN overexpression.",
author = "Zhiwei Dong and Yeo, {Kok Siong} and Gonzalo Lopez and Cheng Zhang and {Dankert Eggum}, {Erin N.} and Rokita, {Jo Lynne} and Ung, {Choong Yong} and Levee, {Taylor M.} and Her, {Zuag Paj} and Howe, {Cassie J.} and Xiaonan Hou and {van Ree}, {Janine H.} and Shuai Li and Shuning He and Ting Tao and Karen Fritchie and Jorge Torres-Mora and Lehman, {Julia S.} and Alexander Meves and Razidlo, {Gina L.} and Rathi, {Komal S.} and Weroha, {S. John} and Look, {A. Thomas} and {van Deursen}, {Jan M.} and Hu Li and Westendorf, {Jennifer J.} and Maris, {John M.} and Shizhen Zhu",
note = "Funding Information: J.H. van Ree reports grants from NIH during the conduct of the study. G.L. Razidlo reports nonfinancial support from Bayer outside the submitted work. S. Weroha reports grants from NIH, Novartis and other support from Kiyatec, Merck, and AstraZeneca outside the submitted work. No disclosures were reported by the other authors. Funding Information: This work was supported by a grant R01 CA240323 (to S. Zhu) from the National Cancer Institute, a V Scholar award (D2018-005) from the V Foundation for Cancer Research (to S. Zhu), and a Platform Grant from the Mayo Center for Biomedical Discovery (to S. Zhu); support from the Mayo Clinic Cancer Center and Center for Individualized Medicine (to S. Zhu); a grant R01 CA1247709, R01 CA180692, and R35 CA220500 (to J.M. Maris) from the NCI. Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",
year = "2021",
month = jun,
day = "1",
doi = "10.1158/0008-5472.CAN-20-1890",
language = "English (US)",
volume = "81",
pages = "2995--3007",
journal = "Cancer Research",
issn = "0008-5472",
number = "11",
}