期刊
CELL
卷 147, 期 3, 页码 554-564出版社
CELL PRESS
DOI: 10.1016/j.cell.2011.09.035
关键词
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资金
- NCI [R01-CA142798-01, R01 CA104348]
- AIDS Malignancy Consortium (AMC)
- Leukemia Research Foundation
- Louis V. Gerstner Foundation
- WLBH Foundation
- Society of MSKCC
- Starr Cancer Consortium [I4-A410]
- NIH MSTP [GM07739, NIH-K08 CA127353]
- ASCO Cancer Foundation
- LLS TRP
- LLS SCOR [S 7032-04]
- LLS scholar
- Burroughs Wellcome Clinical Translational Scientist
- Cancer Center [P30-CA008748]
- Leukemia and Lymphoma Society
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.
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