| Literature DB >> 22036564 |
Elisa Oricchio1, Gouri Nanjangud, Andrew L Wolfe, Jonathan H Schatz, Konstantinos J Mavrakis, Man Jiang, Xiaoping Liu, Joanne Bruno, Adriana Heguy, Adam B Olshen, Nicholas D Socci, Julie Teruya-Feldstein, Frances Weis-Garcia, Wayne Tam, Rita Shaknovich, Ari Melnick, Juha P Himanen, R S K Chaganti, Hans-Guido Wendel.
Abstract
Insights into cancer genetics can lead to therapeutic opportunities. By cross-referencing chromosomal changes with an unbiased genetic screen we identify the ephrin receptor A7 (EPHA7) as a tumor suppressor in follicular lymphoma (FL). EPHA7 is a target of 6q deletions and inactivated in 72% of FLs. Knockdown of EPHA7 drives lymphoma development in a murine FL model. In analogy to its physiological function in brain development, a soluble splice variant of EPHA7 (EPHA7(TR)) interferes with another Eph-receptor and blocks oncogenic signals in lymphoma cells. Consistent with this drug-like activity, administration of the purified EPHA7(TR) protein produces antitumor effects against xenografted human lymphomas. Further, by fusing EPHA7(TR) to the anti-CD20 antibody (rituximab) we can directly target this tumor suppressor to lymphomas in vivo. Our study attests to the power of combining descriptive tumor genomics with functional screens and reveals EPHA7(TR) as tumor suppressor with immediate therapeutic potential.Entities:
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Year: 2011 PMID： 22036564 PMCID： PMC3208379 DOI： 10.1016/j.cell.2011.09.035
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582