β2-adrenergic signalling promotes cell migration by upregulating expression of the metastasis-associated molecule LYPD3

Gruet, M, Cotton, D, Coveney, C ORCID: https://orcid.org/0000-0001-7047-6408, Boocock, DJ ORCID: https://orcid.org/0000-0002-7333-3549, Wagner, S ORCID: https://orcid.org/0000-0002-5221-9851, Komorowski, L, Rees, RC ORCID: https://orcid.org/0000-0002-4574-4746, Pockley, AG ORCID: https://orcid.org/0000-0001-9593-6431, Garner, AC ORCID: https://orcid.org/0000-0003-2488-0623, Wallis, JD ORCID: https://orcid.org/0000-0001-7259-8783, Miles, AK ORCID: https://orcid.org/0000-0002-5388-938X and Powe, DG, 2020. β2-adrenergic signalling promotes cell migration by upregulating expression of the metastasis-associated molecule LYPD3. Biology, 9 (2): 39. ISSN 2079-7737

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Abstract

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line models of basal-type and oestrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and β2-adrenoceptor mediated cell behaviour including migration, invasion, adhesion, and survival in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified biomarkers and drug targets. Baseline levels of adrenoceptor gene expression are higher in basal-type rather than oestrogen receptor-positive cancer cells. Norepinephrine (NE) treatment increased invasive capacity in all cell lines but did not increase proliferation/survival. Protein profiling revealed the upregulation of the pro-metastatic gene Ly6/PLAUR Domain-Containing Protein 3 (LYPD3) in norepinephrine-treated MDA-MB-468 cells. Histology confirmed selective LYPD3 expression in primary and metastatic breast tumour samples. These findings demonstrate that basal-type cancer cells show a more aggressive adrenoceptor-β2-activated phenotype in the resting and stimulated state, which is attenuated by adrenoceptor-β2 inhibition. This study also highlights the first association between ADRβ2 signalling and LYPD3; its knockdown significantly reduced the basal and norepinephrine-induced activity of MCF-7 cells in vitro. The regulation of ADRβ2 signalling by LYPD3 and its metastasis promoting activities, reveal LYPD3 as a promising therapeutic target in the treatment of breast and other cancers.

Item Type:	Journal article
Publication Title:	Biology
Creators:	Gruet, M., Cotton, D., Coveney, C., Boocock, D.J., Wagner, S., Komorowski, L., Rees, R.C., Pockley, A.G., Garner, A.C., Wallis, J.D., Miles, A.K. and Powe, D.G.
Publisher:	MDPI AG
Date:	22 February 2020
Volume:	9
Number:	2
ISSN:	2079-7737
Identifiers:	Number Type 10.3390/biology9020039 DOI 1296415 Other
Rights:	© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	28 Feb 2020 09:38
Last Modified:	24 Jun 2021 15:04
URI:	https://irep.ntu.ac.uk/id/eprint/39324

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