Silencing SOX2 Induced Mesenchymal-Epithelial Transition and Its Expression Predicts Liver and Lymph Node Metastasis of CRC Patients

Abstract

SOX2 is an important stem cell marker and plays important roles in development and carcinogenesis. However, the role of SOX2 in Epithelial-Mesenchymal Transition has not been investigated. We demonstrated, for the first time, that SOX2 is involved in the Epithelial-Mesenchymal Transition (EMT) process as knock downof SOX2 in colorectal cancer (CRC) SW620 cells induced a Mesenchymal-Epithelial Transition (MET) process with recognized changes in the expression of key genes involved in the EMT process including E-cadherin and vimentin. In addition, we provided a link between SOX2 activity and the WNT pathway by showing that knock down of SOX2 reduced the WNT pathway activity in colorectal cancer (CRC) cells. We further demonstrated that SOX2 is involved in cell migration and invasion in vitro and in metastasis in vivo for CRC cells, and that the process might be mediated through the MMP2 activity. Finally, an IHC analysis of 44 cases of colorectal cancer patients suggested that SOX2 is a prognosis marker for metastasis of colorectal cancers.

SOX2 Targets Fibronectin 1 to Promote Cell Migration and Invasion in Ovarian Cancer: New Molecular Leads for Therapeutic Intervention

“…Increased invasion might be related to the increased MMP2 and MMP9 proteolytic activities induced by SOX2 overexpression (Fig. 5D), a phenomenon we also observed in colorectal cancer cells (Han et al, 2012). Matrix metalloproteases (MMPs) are known to play essential roles in cell migration, differentiation, angiogenesis, apoptosis, and host defenses (Seiki, 2002).…”

“…5A). We previously showed that SOX2 regulated the epithelial to mesenchymal transition (EMT) in colorectal cancer cells (Han et al, 2012). Therefore, we assessed the expression of vimentin, which is a marker protein of mesenchymal cells, to examine if the morphological changes represented the EMT process.…”

“…Most studies to date have found that SOX2 plays a role in promoting cancer. For example, the downregulation of SOX2 expression resulted in decreased tumor cell proliferation and colony formation in breast cancer (Stolzenburg et al, 2012), and the knockdown of SOX2 markedly suppressed invasion and metastasis of prostate cancer (Bae et al, 2011), colorectal cancer (Han et al, 2012), and gliomas (Alonso et al, 2011). However, the tumor suppressive role of SOX2 was reported in gastric cancer, in which the expression of SOX2 is frequently downregulated, and SOX2 inhibits cell growth through cell cycle arrest and apoptosis (Otsubo et al, 2011).…”

Expression of SOX2 in oral squamous cell carcinoma and the association with lymph node metastasis

“…Epithelial cells gain polarity and motility during EMT, which are necessary for tumor invasion and metastasis in various types of epithelial carcinomas. Notably, studies have identified that knocking down SOX2 promoted MET and resulted in the translocation of β-catenin, which is critical in the WNT pathway (92). Studies indicated that all SOX2-positive primary tumors retained a SOX2-expressing phenotype during lymph node metastasis.…”

Role of stem cells in large bowel carcinogenesis

“…Одновременно компоненты Wnt-сигнального пути в ядре рекрутируют больше β-катенина, активи-руют Wnt-путь и его мишени. Sox2 также увеличивает активность Wnt-пути за счет уменьшения LEF/TCF-активности и экспрессии хорошо известных генов-мишеней циклина D1 и c-Myc в клетках с уменьшенной транскрипцией Sox2 [38]. Существующая взаимосвязь между EMT и Sox2 не удивительна, поскольку EMT яв-ляется ключевым процессом в развитии эмбриона, а Sox2 играет ключевую роль в развитии и формировании тка-ней и органов на ранних этапах эмбриогенеза [39].…”