Type

Journal Article

Authors

Michael J Duffy
Norma O'Donovan
John Crown
Stephen F Madden
Susan A Kennedy
Patricia M McGowan
Maeve Mullooly

Subjects

Biochemistry

Topics
cancer cell lines rna interference cell migration inhibitor adam10 triple negative breast cancer cancer invasion cell invasion invasion targeted therapy migration oestrogen receptor breast cancer

ADAM10: a new player in breast cancer progression? (2015)

Abstract The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin. As cleavage of several of these proteins has been implicated in cancer formation and progression, we hypothesised that ADAM10 is also involved in these processes. ADAM10 expression was decreased by RNA interference and the effects of this on cell numbers, invasion and migration were determined. We also examined the effect of ADAM10 inhibition on breast cancer cell line invasion and migration. Using the triple-negative (TN) breast cancer cell lines, BT20, MDA-MB-231 and the non-TN cell line MDA-MB-453, knockdown of ADAM10 expression significantly decreased in vitro migration (P<0.01; for each cell line). Similarly, treatment with the ADAM10-selective inhibitor GI254023X reduced migration in the three cell lines (for BT20, P<0.001; for MDA-MB-231, P=0.005; for MDA-MB-453, P=0.023). In contrast, neither knockdown of ADAM10 nor treatment with the ADAM10-selective inhibitor GI254023X significantly affected cell numbers. Using extracts of primary breast cancers, higher levels of ADAM10 were found more frequently in high-grade vs low-grade tumours (P<0.001) and in oestrogen receptor (ER)-negative compared with ER-positive tumours (P=0.005). Analysis of pooled publicly available data sets found that high levels of ADAM10 mRNA were associated with adverse outcome in patients with the basal subtype of breast cancer. Based on our combined cell line and breast cancer extract data, we conclude that ADAM10 is likely to be involved in breast cancer progression, especially in the basal subtype.
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Ireland -> University College Dublin -> Systems Biology Ireland
Ireland -> University College Dublin -> SBI Research Collection
Ireland -> Dublin City University -> PubMed
Ireland -> University College Dublin -> Medicine Research Collection
Ireland -> University College Dublin -> College of Health and Agricultural Sciences
Ireland -> University College Dublin -> School of Medicine
Ireland -> University College Dublin -> Conway Institute
Ireland -> University College Dublin -> Institutes and Centres

Full list of authors on original publication

Michael J Duffy, Norma O'Donovan, John Crown, Stephen F Madden, Susan A Kennedy, Patricia M McGowan, Maeve Mullooly

Experts in our system

1
Michael J Duffy
University College Dublin
 
2
Norma O'Donovan
Dublin City University
Total Publications: 59
 
3
John Crown
Dublin City University
Total Publications: 104
 
4
Stephen F Madden
Dublin City University
Total Publications: 45
 
5
Patricia M McGowan
Dublin City University
Total Publications: 8
 
6
Maeve Mullooly
University College Dublin