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.
|Original language||English (US)|
|Number of pages||11|
|Journal||International Journal of Biochemistry and Cell Biology|
|State||Published - Jul 1 2016|
Bibliographical noteFunding Information:
This research was partially supported by the Australian National Health and Medical Research Council (NHMRC; project grant 1022263 ) and the Queensland Pharmacy Research Trust . TAS was funded by an NHMRC Biomedical Postgraduate Scholarship ( 1039358 ). EWT was supported in part by the EMP athy Breast Cancer Network, a national collaborative research program of the National Breast Cancer Foundation (GC-10-04).
© 2016 Elsevier Ltd. All rights reserved.
- Breast cancerEpidermal growth factor
- Epithelial-mesenchymal transition
- Janus kinase
- Src family kinase