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Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells

Citation

Stewart, TA and Azimi, I and Brooks, AJ and Thompson, EW and Roberts-Thomson, SJ and Monteith, GR, Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells, The international journal of biochemistry & cell biology, 76 pp. 64-74. ISSN 1357-2725 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 Elsevier Ltd.

DOI: doi:10.1016/j.biocel.2016.05.007

Abstract

Epithelial-mesenchymal transition (EMT) is an important process associated with the metastasis of breast cancer cells. Members of the Janus kinases (JAKs) and Src family kinases (SFKs) are implicated in the regulation of an invasive phenotype in various cancer cell types. Using the pharmacological inhibitors JAK Inhibitor I (a pan-JAK inhibitor) and PP2 we investigated the role of the JAKs and SFKs, respectively, in the regulation of EMT markers in the MDA-MB-468 breast cancer cell line model of epidermal growth factor (EGF)-induced EMT. We identified selective inhibition of EGF induction of the mesenchymal marker vimentin by PP2 and JAK Inhibitor I. The effect of JAK Inhibitor I on vimentin protein induction occurred at a concentration lower than that required to significantly inhibit EGF-mediated signal transducer and activator of transcription 3 (STAT3)-phosphorylation, suggesting involvement of a STAT3-independent mechanism of EGF-induced vimentin regulation by JAKs. Despite our identification of a role for the JAK family in EGF-induced vimentin protein expression, siRNA-mediated silencing of each member of the JAK family was unable to phenocopy pharmacological inhibition, indicating potential redundancy among the JAK family members in this pathway. While SFKs and JAKs do not represent global regulators of the EMT phenotype, our findings have identified a role for members of these signaling pathways in the regulation of EGF-induced vimentin expression in the MDA-MB-468 breast cancer cell line.

Item Details

Item Type:Refereed Article
Keywords:Breast cancer; Epidermal growth factor; Epithelial-mesenchymal transition; Janus kinase; Src family kinase
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Cell Biology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Azimi, I (Dr Iman Azimi)
ID Code:124406
Year Published:2016
Web of Science® Times Cited:3
Deposited By:Pharmacy
Deposited On:2018-02-21
Last Modified:2018-04-11
Downloads:0

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