ADAM10: a new player in breast cancer progression?

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Title: ADAM10: a new player in breast cancer progression?
Authors: Mullooly, Maeve
McGowan, Patricia M.
Kennedy, Susan A.
Duffy, Michael J.
et al.
Permanent link: http://hdl.handle.net/10197/9782
Date: 18-Aug-2015
Online since: 2019-04-03T08:44:14Z
Abstract: Background: 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. Methods: 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. Results: 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 (Po0.01; for each cell line). Similarly, treatment with the ADAM10-selective inhibitor GI254023X reduced migration in the three cell lines (for BT20, Po0.001; for MDA-MB-231, P ¼ 0.005; for MDA-MB-453, P ¼ 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 (Po0.001) and in oestrogen receptor (ER)-negative compared with ERpositive tumours (P ¼ 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. Conclusions: 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.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Health Research Board
Irish Cancer Society
Science Foundation Ireland
Type of material: Journal Article
Publisher: Cancer Research UK
Journal: British Journal of Cancer
Volume: 113
Start page: 945
End page: 951
Copyright (published version): 2015 the Authors
Keywords: ADAM10Breast cancerMigrationInvasionInhibitorTargeted therapy
DOI: 10.1038/bjc.2015.288
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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