The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma

Elisa Oricchio, 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

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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.

Original languageEnglish (US)
Pages (from-to)554-564
Number of pages11
JournalCell
Volume147
Issue number3
DOIs
StatePublished - Oct 28 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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. (2011). The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma. Cell, 147(3), 554-564. https://doi.org/10.1016/j.cell.2011.09.035