Journal article
Src Stimulates Fibroblast Growth Factor Receptor-2 Shedding by an ADAM15 Splice Variant Linked to Breast Cancer
Cancer research (Chicago, Ill.), Vol.69(11), pp.4573-4576
2009
DOI: 10.1158/0008-5472.CAN-08-4766
PMID: 19487280
Abstract
ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice variant affects the function of ADAM15. Here, we show that ADAM15B has enhanced catalytic activity in cell-based assays compared with ADAM15A, which lacks a Src-binding site, using shedding of fibroblast growth factor receptor 2iiib variant as an assay for catalytic activity. Moreover, the enhanced activity of ADAM15B compared with ADAM15A depends on Src because it is abolished by Src-kinase inhibitors and in Src−/− cells, but not in Src−/− cells rescued with Src. These findings provide insights into the mechanism of how a splice variant linked to clinical agressiveness in breast cancer causes increased activity of ADAM15B, and suggest that inhibitors of the ADAM15 protease activity or of the interaction of ADAM15B with Src could be useful to treat breast cancer in patients with dysregulated ADAM15B
Details
- Title: Subtitle
- Src Stimulates Fibroblast Growth Factor Receptor-2 Shedding by an ADAM15 Splice Variant Linked to Breast Cancer
- Creators
- Thorsten MARETZKY - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, United StatesSylvain M LE GALL - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, United StatesSusanne WORPENBERG-PIETRUK - Protease Platform, Novartis Institutes for Biomedical Research, Basel, SwitzerlandJörg ELDER - Protease Platform, Novartis Institutes for Biomedical Research, Basel, SwitzerlandChristopher M OVERALL - Departments of Oral Biological and Medical Sciences, and Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, CanadaXin-Yun HUANG - Department of Physiology, Weill Medical College of Cornell University, New York, New York, United StatesZaruhi POGHOSYAN - Department of Pathology, School of Medicine, Cardiff University, Heath Park, Cardiff, United KingdomDylan R EDWARDS - School of Biological Sciences, Biomedical Research Centre, University of East Anglia, Norwich Research Park, Norwich, United KingdomCarl P BLOBEL - Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.69(11), pp.4573-4576
- DOI
- 10.1158/0008-5472.CAN-08-4766
- PMID
- 19487280
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- American Association for Cancer Research
- Language
- English
- Date published
- 2009
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984094393502771
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