The Roles of SOX9 in Oral Cancer Progression
Date Issued
2012
Date
2012
Author(s)
Wang, Ting-yi
Abstract
Epidemiological studies have indicated that the oral cancer incidence in Taiwan is closely related to the habit of betel nut chewing. At present, the population of betel nut chewing has reach over two million in Taiwan. The mortality and incidence of oral cancer are ranked the fifth leading cancer in male, and the annual growth rate of oral cancer is also the highest in Taiwan. SOX9 (Sry-related HMG box 9) is an important transcription factor that plays important roles in embryogenesis and tissue differentiation. Previous studies showed that SOX-9 was significantly higher in oral cancer than that in normal oral mucosa. The expression of SOX-9 was correlated with advanced tumor stage, lymph node metastasis and short survival time. However, the role of SOX9 in oral cancer tumor progression is still unclear. In this study, SOX-9 over-expressed and shRNA stably-transfected cells were established to investigate migration/invasion ability in vitro and tumorigenesis and progression in vivo. We found that alterations in the SOX-9 level in OSCC cell lines positively modulated their invasive ability but not growth. Animal model also showed that SOX-9 overexpression had higher distant lymph node metastasis rate. Microarray analysis of gene expression in SOX-9 knockout TW2.6 cells identified dysregulation of many genes involved in metastasis. In particular, we knock-down KRT19 by shRNA and restored migration and invasion abilities in Tw2.6/shSOX9 cells. The KRT19 expression in OSCC specimens were examined by immunohistochemistry. KRT19 expression is higher in the patients with early stage, and lower in the patients with late stage. These results indicated that SOX9 influences cancer cell migration and invasion capacities through regulating KRT19.
Subjects
Oral cancer
Migration
Invasion
SDGs
Type
thesis
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