The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma Journal Article
| Authors: | Oricchio, E.; Nanjangud, G.; Wolfe, A. L.; Schatz, J. H.; Mavrakis, K. J.; Jiang, M.; Liu, X.; Bruno, J.; Heguy, A.; Olshen, A. B.; Socci, N. D.; Teruya-Feldstein, J.; Weis-Garcia, F.; Tam, W.; Shaknovich, R.; Melnick, A.; Himanen, J. P.; Chaganti, R. S. K.; Wendel, H. G. |
| Article Title: | The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma |
| 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 (EPHA7TR) interferes with another Eph-receptor and blocks oncogenic signals in lymphoma cells. Consistent with this drug-like activity, administration of the purified EPHA7TR 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 EPHA7TR as tumor suppressor with immediate therapeutic potential. © 2011 Elsevier Inc. |
| Keywords: | controlled study; human tissue; nonhuman; rituximab; animal cell; mouse; animals; mice; animal experiment; animal model; rna interference; in vivo study; cell line, tumor; disease model; protein purification; murinae; transplantation, heterologous; genomics; chromosomes, human, pair 6; neoplasm transplantation; protein variant; follicular lymphoma; lymphoma, follicular; genes, tumor suppressor; antibodies, monoclonal, murine-derived; ephrin receptor a7; receptor, epha7 |
| Journal Title: | Cell |
| Volume: | 147 |
| Issue: | 3 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2011-10-28 |
| Start Page: | 554 |
| End Page: | 564 |
| Language: | English |
| DOI: | 10.1016/j.cell.2011.09.035 |
| PROVIDER: | scopus |
| PMCID: | PMC3208379 |
| PUBMED: | 22036564 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 9 December 2011" - "CODEN: CELLB" - "Source: Scopus" |
