Dataset Information

Protein profiling of stress-activated breast cancer cell models

ABSTRACT: This study provides insights into the efficacy of beta-blockers as breast cancer therapeutics.Cell line models of basal-type and estrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and ADRβ2-mediated cell behaviour including migration, invasion, adhesion, and proliferation in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified response biomarkers and drug targets. Protein profiling revealed the upregulation of the pro-metastatic gene LYPD3 in norepinephrine treated MDA MB 468 cells. Histology confirmed selective LYPD3 expression in clinical primary and metastatic breast tumours. These findings demonstrate that basal-type cancer models show a more aggressive ADRβ2-activated phenotype in the resting and stimulated state, which is attenuated by ADRβ2 inhibition, and explain some of the previous studies that have cast doubt on the value of beta-blocker therapy in breast cancer. These findings suggest that propranolol should be clinically evaluated in patients with basal-type tumours expressing high levels of ADRβ2 and LYPD3.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Amanda Miles

LAB HEAD: David J Boocock

PROVIDER: PXD009488 | Pride | 2020-05-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MDA231_Lysate_ICI_1_SWATH.wiff	Wiff
	MDA231_Lysate_ICI_1_SWATH.wiff.scan	Wiff
	MDA231_Lysate_ICI_2_SWATH.wiff	Wiff
	MDA231_Lysate_ICI_2_SWATH.wiff.scan	Wiff
	MDA231_Lysate_ICI_3_SWATH.wiff	Wiff

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Publications

β2-Adrenergic Signalling Promotes Cell Migration by Upregulating Expression of the Metastasis-Associated Molecule LYPD3.

Gruet Michael M Cotton Daniel D Coveney Clare C Boocock David J DJ Wagner Sarah S Komorowski Lucie L Rees Robert C RC Pockley A Graham AG Garner A Christopher AC Wallis John D JD Miles Amanda K AK Powe Desmond G DG

Biology 20200222 2

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 ...[more]

PMID: 32098331

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