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

Stewart, Teneale A., Azimi, Iman, Brooks, Andrew J., Thompson, Erik W., Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2016) 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 and Cell Biology, 76 64-74. doi:10.1016/j.biocel.2016.05.007

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Author Stewart, Teneale A.
Azimi, Iman
Brooks, Andrew J.
Thompson, Erik W.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Title Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells
Journal name The International Journal of Biochemistry and Cell Biology   Check publisher's open access policy
ISSN 1878-5875
1357-2725
Publication date 2016-07-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.biocel.2016.05.007
Open Access Status File (Author Post-print)
Volume 76
Start page 64
End page 74
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Pergamon Press
Language eng
Subject 1303 Biochemistry
1307 Cell Biology
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 JAIL 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 JAIL 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 JAM family in EGF-induced vimentin protein expression, siRNA-mediated silencing of each member of the JAM family was unable to phenocopy pharmacological inhibition, indicating potential redundancy among the JAM 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. (C) 2016 Elsevier Ltd. All rights reserved.
Formatted 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.
Keyword Epithelial-Mesenchymal Transition
Epidermal-Growth-Factor
Gene-Expression
Carcinoma Cells
Factor Receptor
Signaling Pathway
Lung-Cancer
In-Vivo
Constitutive Activation
Pancreatic-Cancer
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1022263
1039358
GC-10-04
Institutional Status UQ

 
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