TitleThe Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma.
Publication TypeJournal Article
Year of Publication2011
AuthorsOricchio, Elisa, Nanjangud Gouri, Wolfe Andrew L., Schatz Jonathan H., Mavrakis Konstantinos J., Jiang Man, Liu Xiaoping, Bruno Joanne, Heguy Adriana, Olshen Adam B., Socci Nicholas D., Teruya-Feldstein Julie, Weis-Garcia Frances, Tam Wayne, Shaknovich Rita, Melnick Ari, Himanen Juha P., Chaganti R S. K., and Wendel Hans-Guido
Date Published2011 Oct 28
KeywordsAnimals, Antibodies, Monoclonal, Murine-Derived, Cell Line, Tumor, Chromosomes, Human, Pair 6, Genes, Tumor Suppressor, Genomics, Humans, Lymphoma, Follicular, Male, Mice, Neoplasm Transplantation, Receptor, EphA7, Rituximab, RNA Interference, Transplantation, Heterologous

<p>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.</p>

Alternate JournalCell
PubMed ID22036564
PubMed Central IDPMC3208379
Grant ListGM07739 / GM / NIGMS NIH HHS / United States
R01-CA142798-01 / CA / NCI NIH HHS / United States
K08 CA127353 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 CA142798 / CA / NCI NIH HHS / United States
P30-CA008748 / CA / NCI NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
R01 CA142798-01 / CA / NCI NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States