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Updated: Jul 13, 2026

Three-Dimensional (3D) Tumor Spheroid Invasion Assay
Published on: May 1, 2015
Three-dimensional regulatory hubs support oncogenic programs in glioblastoma
Sarah L Breves1, Dafne Campigli Di Giammartino2, James Nicholson3
1Sanford I. Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Physiology, Biophysics and Systems Biology Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY, USA; Department of Surgery, New York-Presbyterian Hospital, Weill Cornell Medicine, New York, NY, USA; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY, USA.
None:
Dysregulation of enhancer-promoter communication in the three-dimensional (3D) nucleus is increasingly recognized as a potential driver of oncogenic programs. Here, we profiled the 3D enhancer-promoter networks of patient-derived glioblastoma stem cells to identify central regulatory nodes. We focused on hyperconnected 3D hubs and demonstrated that hub-interacting genes exhibit high and coordinated expression at the single-cell level and are associated with oncogenic programs that distinguish glioblastoma from low-grade glioma. Epigenetic silencing of a recurrent hub-with an uncharacterized role in glioblastoma-was sufficient to cause downregulation of hub-connected genes, shifts in transcriptional states, and reduced clonogenicity. Integration of datasets across 16 cancers identified "universal" and cancer-type-specific 3D hubs that enrich for oncogenic programs and factors associated with worse prognosis. Genetic alterations could explain only a small fraction of hub hyperconnectivity and increased activity. Overall, our study provides strong support for the potential central role of 3D regulatory hubs in controlling oncogenic programs and properties.
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