The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma

Elisa Oricchio; Gourd Nanjangud; Andrew L Wolfe; Jonathan H Schatz; Konstantinos J Mavrakis; Man Jiang; Xiaoping Liu; Joanne Bruno; Adriana Heguy; Adam B Olshen; Nicholas D Socci; J Teruya-Feldstein; Frances Weis-Garcia; Wayne Tam; Rita Shaknovich; Ari Melnick; Juha P Himanen; R.S.K Chaganti; Hans-Guido Wendel

doi:10.1016/j.cell.2011.09.035

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The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma

Journal article

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The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma

Elisa Oricchio, Gourd Nanjangud, Andrew L Wolfe, Jonathan H Schatz, Konstantinos J Mavrakis, Man Jiang, Xiaoping Liu, Joanne Bruno, Adriana Heguy, Adam B Olshen, …

Cell (Cambridge), Vol.147(3), pp.554-564

2011-10-28

DOI: https://doi.org/10.1016/j.cell.2011.09.035

PMCID: PMC3208379

PMID: 22036564

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 anti-tumor 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.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.130 Lymphomas; 1.130.132 Lymphoma
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology
ESI research areas: Molecular Biology & Genetics

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Title: The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma
Creators: Elisa Oricchio - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Gourd Nanjangud - Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Andrew L Wolfe - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Jonathan H Schatz - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Konstantinos J Mavrakis - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Man Jiang - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Xiaoping Liu - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Joanne Bruno - Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program, New York, NY 10065
Adriana Heguy - Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Adam B Olshen - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Nicholas D Socci - Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
J Teruya-Feldstein - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Frances Weis-Garcia - Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Wayne Tam - Department of Pathology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065
Rita Shaknovich - Division of Hematology/Oncology, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065
Ari Melnick - Division of Hematology/Oncology, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065
Juha P Himanen - Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
R.S.K Chaganti - Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Hans-Guido Wendel - Cancer Biology & Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
Publication Details: Cell (Cambridge), Vol.147(3), pp.554-564
Grant note: R01 CA142798-01 || CA / National Cancer Institute : NCI
Academic Unit: Miller School of Medicine; UMMG Dept of Medicine - Hematology/Oncology
Language: English
Resource Type: Journal article
PMID: 22036564
PMCID: PMC3208379
Record Identifier: 991031614897502976