title: Transcriptional profiling identifies upregulated genes following induction of epithelial-mesenchymal transition in squamous carcinoma cells.
abstract: During the progression of head and neck squamous cell carcinoma (HNSCC), the induction of an epithelial-mesenchymal transition (EMT) program may play a critical role in the dissemination of cells from the primary tumor to distant metastatic foci. The process of EMT involves the activation of several important genes and pathways to help maintain survival and growth and evolve into highly invasive and metastatic variants. In this study, expression microarray analysis identified a set of 145 upregulated genes in EMT-like HNSCC cells. Some of the strongly upregulated transcripts include genes that are reportedly involved in invasion and metastasis, such as DOCK10, LOX, ROBO1 and SRGN. Importantly, the Tbx3 gene, a member of the T-box transcription factor, was strongly upregulated in SCC cells displaying an EMT-like phenotype compared to cells with an epitheloid, non-EMT behavior. Tbx3 was also found to be strongly upregulated at the protein and gene expression level in an experimental model of snail-induced EMT cells. In addition, siRNA-induced Tbx3 depletion modestly suppressed cell invasion while enhancing Tbx3-mediated resistance to anoikis. Our findings provide evidence that Tbx3 overexpression promotes SCC cell survival displaying an EMT phenotype. This set of newly identified genes that are modulated during EMT-like conversion may be important diagnostic biomarkers during the process of HNSCC progression.
authors.affiliation: Department of Cell and Tissue Biology, School of Dentistry, 521 Parnassus Avenue, University of California at San Francisco, San Francisco, CA 94143, USA. joseph.humtsoe@ucsf.edu
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Humtsoe
authors.forename: Eriko
authors.initials: E
authors.lastname: Koya
authors.forename: Eric
authors.initials: E
authors.lastname: Pham
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Aramoto
authors.forename: Jian
authors.initials: J
authors.lastname: Zuo
authors.forename: Tohru
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Randall H
authors.initials: RH
authors.lastname: Kramer
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D052138:Genes, Neoplasm / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness; D000077195:Squamous Cell Carcinoma of Head and Neck; D020825:T-Box Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation; D054928:Validation Studies as Topic
chemical_list: D020825:T-Box Domain Proteins; C106884:TBX3 protein, human