Crosstalk Between EMT And Stemness State In EsophagealSquamous Cell Carcinoma

Epithelial-mesenchymal transition (EMT) is crucial for specific morphogenetic movements duringembryonic development as well as pathological processes of tumor cell invasion and metastasis.TWIST1, as a highly conserved member of the basic helix-loop-helix (bHLH) transcription factors,plays key roles in EMT for either embryogenesis or tumorigenesis. SOX2 is an important keytranscription factor involved in self-renewal and pluripotency characteristics of undifferentiatedembryonic stem cells. Our aim in this study was to elucidate probable crosstalk between thesefactors. Expression pattern of TWIST1 and SOX2 was analyzed in 55 ESCC patients using relativecomparative Real-time PCR. In silico analysis of the SOX2 gene was performed. Using a retroviralsystem, KYSE30 cells were transduced to ectopically express TWIST1, followed by qRT-PCR toelucidate the regulatory role of TWIST1 on SOX2 gene expression. Co-overexpression of TWIST1 andSOX2 was detected in ESCC patients significantly (p10.05). The TWIST1 transduced KYSE30 cellsshowed significantly high level of TWIST1 expression compared to control cells. Enforcedexpression of TWIST1 in KYSE30 dramatically increased SOX2 gene expression. Direct correlationbetween TWIST1 and SOX2 mRNA levels may introduce novel molecular gene expression pathwayconnecting EMT process and stemness state of tumor cells during ESCC aggressiveness andtumorigenesis. Consequently, these data extend the spectrum of biological activities of TWIST1 andpropose that therapeutic repression of TWIST1 may be an effective strategy to inhibit cancer stemcell characteristics.