title: Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells.
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.
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Teneale A
authors.initials: TA
authors.lastname: Stewart
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia; Mater Research, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Iman
authors.initials: I
authors.lastname: Azimi
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia; The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brooks
authors.affiliation: Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia; Australia and Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Thompson
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Roberts-Thomson
authors.affiliation: School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia; Mater Research, Translational Research Institute, The University of Queensland, Brisbane, QLD, Australia. Electronic address: gregm@uq.edu.au.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Monteith
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014746:Vimentin / Q000096:biosynthesis* / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D014746:Vimentin; D004815:Epidermal Growth Factor; D053612:Janus Kinases; D019061:src-Family Kinases
keywords: Breast cancer; Epidermal growth factor; Epithelial-mesenchymal transition; Janus kinase; Src family kinase