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Intersectin 1 is required for neuroblastoma tumorigenesis

Oncogene volume 31, pages 4828–4834 (2012)Cite this article

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Abstract

Intersectin 1 (ITSN1) is a scaffold protein that regulates diverse cellular pathways, including endocytosis and several signal transduction pathways, including phosphatidylinositol 3-kinase, Class IIβ (PI3K-C2β). ITSN1's transforming potential in vitro suggests that this scaffold protein may be involved in human tumorigenesis. Herein, we demonstrate that ITSN1 is expressed in primary human neuroblastoma tumors and tumor cell lines and is necessary for their in vitro and in vivo tumorigenic properties. Silencing ITSN1 significantly inhibits the anchorage independent growth of tumor cells in vitro and tumor formation in xenograft assays independent of MYCN status. Overexpression of the ITSN1 target, PI3K-C2β, rescues the soft agar growth of ITSN1-silenced cells demonstrating the importance of the ITSN1-PI3K-C2β pathway in neuroblastoma tumorigenesis. These findings represent the first demonstration that the ITSN1-PI3K-C2β pathway has a requisite role in human cancer, specifically neuroblastomas.

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Acknowledgements

We thank Naohiko Ikegaki and Bernard Weissman for providing various neuroblastoma cell lines, and Drs Michael Hogarty and Wendy London and the Children's Oncology Group ANBL00B1 Neuroblastoma Biology Studies for providing the primary neuroblastoma tumor samples for analysis. We also thank Dr Ikegaki for providing advice on the xenograft assay, Dr Javed Khan for his helpful discussions regarding the Oncogenomics database, and members of the O’Bryan lab for comments on the manuscript. These studies were supported by grants to JPO from the National Institutes of Health (HL090651), Department of Defense (PR080428), the Foundation Jerome Lejeune, and the St Baldrick's Foundation.

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  1. Department of Pharmacology, University of Illinois at Chicago, Chicago, IL, USA

    A Russo & J P O'Bryan

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Correspondence to J P O'Bryan.

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Russo, A., O'Bryan, J. Intersectin 1 is required for neuroblastoma tumorigenesis. Oncogene 31, 4828–4834 (2012). https://doi.org/10.1038/onc.2011.643

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