上皮ケラチノサイトのフェノタイプ変化における転写因子SOX4の役割

<p>SOX4 is a member of the SOX (Sex-determining region Y-related high-mobility group box) family of transcription factors, and known to associated with the promotion of epithelial cell tumorigenesis, invasion, and metastasis. However, the role of SOX4 in epithelial keratinocytes remains elusive. In this study, we aim to investigate the involvement of SOX4 in the phenotypic changes and functional regulation of a human keratinocyte cell line (HaCaT).Firstly, we generated a SOX4 overexpressing cell line (Tet on SOX4 HaCaT) in which SOX4 expression is induced in the presence of doxycycline (Dox). Dox treatment impaired intercellular contact and altered the cells to exhibit a protruding morphology. Moreover, phalloidin staining revealed an increase in filopodia (filamentous cell membrane extensions by fibrous actin bundles)-like structures. qRT-PCR and western blotting revealed that SOX4 decreased the expression of epithelial markers (KRT13, CLDN1) and increased the expression of mesenchymal markers (Vim, FN1). Because the gene profiles may have been significantly altered, we performed comprehensive RNA sequencing analysis. Gene clustering and gene ontology analyses of differentially expressed genes revealed that Dox treatment of Tet on SOX4 HaCaT increased the expression of genes related to the cytoskeleton such as actin fiber formation and actin skeletal regulation. These findings indicate that SOX4 induces EMT-like phenotypic and cytoskeletal changes in epithelial keratinocytes.</p>