University Of Tasmania

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Assessment of Janus protein tyrosine kinases as potential regulators of epithelial-mesenchymal transition using a model of epidermal growth factor induced breast cancer epithelial-mesenchymal transition [Poster]

conference contribution
posted on 2023-05-24, 21:14 authored by Bassett, JJ, Stewart, TA, Iman AzimiIman Azimi, Davis, FM, Thompson, EW, Brooks, AJ, Roberts-Thomson, SJ, Monteith, GR

Introduction: Epithelial-mesenchymal transition (EMT) is the process of epithelial cells acquiring a mesenchymal phenotype, with increased migratory and invasive properties, and is thought to be involved in metastasis. Regulators of EMT may represent novel therapeutic targets in invasive breast cancer subtypes. Previously we have implicated calcium signalling in the activation of signal transducer and activator of transcription 3 (STAT3) and the expression of specific EMT markers in a MDA-MB-468 breast cancer cell line model of epidermal growth factor (EGF) induced EMT. However, the exact mechanism of this regulation is unknown.

Aims: To investigate upstream regulators of STAT3 activation and their role in the expression of the EMT marker vimentin using a model of EMT in MDA-MB-468 breast cancer cells.

Methods: MDA-MB-468 cells were pre-treated for 1 h with the pan Janus tyrosine kinase (JAK) inhibitor, JAK inhibitor I (1, 10 μM) or the Src family tyrosine kinase inhibitor, PP2 (0.1, 1, 10 μM). Total cellular protein was isolated following stimulation with EGF (50 ng/mL) for 10-20 min and levels of the activated, phosphorylated STAT3 were analysed using immunoblotting. Vimentin protein and mRNA expression was assessed 24 h after EGF treatment (50 ng/mL) in the presence or absence of JAK inhibitor I or PP2. Vimentin protein was assessed using immunoblotting and vimentin RNA using real time RT-PCR.

Results: Both JAK inhibitor I and PP2 significantly decreased EGF-induced STAT3 phosphorylation. JAK inhibitor I also appeared to decrease vimentin protein and mRNA expression at 24 h.

Discussion: Using the MDA-MB-468 model of EGF-induced EMT we have identified a potential role for Janus protein tyrosine kinases in the upstream regulation of STAT3 phosphorylation and vimentin expression. Further studies will be undertaken to identify the specific JAK isoforms involved and the intricacies of the relationship with calcium transporters


Publication title

ASCEPT-MPGPCR Joint Scientific Meeting




School of Pharmacy and Pharmacology

Place of publication


Event title

ASCEPT-MPGPCR Joint Scientific Meeting

Event Venue

Melbourne, Australia

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Date of Event (End Date)


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Socio-economic Objectives

Expanding knowledge in the health sciences