title: SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
abstract: The epithelial to mensenchymal transition program regulates various aspects of embryonic development and tissue homeostasis, but aberrant activation of this pathway in cancer contributes to tumor progression and metastasis. TGF-b potently induces an epithelial to mensenchymal transition in cancers of epithelial origin by inducing transcriptional changes mediated by several key transcription factors. Here, we identify the developmental transcription factor SOX4 as a transcriptional target of TGF-b in immortalized human mammary epithelial cells. SOX4 expression and activity are rapidly induced in the early stages of the TGF-b-induced epithelial to mensenchymal transition. We demonstrate that conditional activation of Sox4 is sufficient to induce the expression of N-cadherin and additional mesenchymal markers including vimentin and fibronectin, but fails to induce complete EMT as no changes are observed in the expression of E-cadherin and b-catenin. Moreover, shRNA-mediated knockdown of SOX4 significantly delays TGF-b-induced mRNA and protein expression of mesenchymal markers. Taken together, these data suggest that TGF-b-mediated increased expression of SOX4 is required for the induction of a mesenchymal phenotype during EMT in human mammary epithelial cells.
authors.affiliation: Department of Cell Biology, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Stephin J
authors.initials: SJ
authors.lastname: Vervoort
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Lourenço
authors.forename: Ruben
authors.initials: R
authors.lastname: van Boxtel
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coffer
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D005353:Fibronectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D016212:Transforming Growth Factor beta; D014746:Vimentin