Abstract
Gliomas are brain and spinal cord malignancies characterized by high malignancy, high recurrence and poor prognosis, the underlying mechanisms of which remain largely elusive. Here, we found that the Sry-related high mobility group box (Sox) family transcription factor, Sox9, was upregulated and correlated with poor prognosis of clinical gliomas. Sox9 promotes migration and invasion of glioma cells and in vivo development of xenograft tumors from inoculated glioma cells. Sox9 functions downstream of the transforming growth factor-β (TGF-β) pathway, in which TGF-β signaling prevent proteasomal degradation of the Sox9 protein in glioma cells. These findings provide novel insight into the wide interplay between TGF-β signaling and oncogenic transcription factors, and have implications for targeted therapy and prognostic assessment of gliomas.
Highlights
Glioma is the most common primary central nervous system (CNS) malignant tumor, accounting for about 35–40% of intracranial tumors
We found here that Sox9, a transcription factor commonly overexpressed in various glioma and glioblastoma, is upregulated by transforming growth factor-b (TGF-b) signaling
Consistent with previous reports in chondrocytes [19, 30], we established that the regulation occurs in the posttranslational level, i.e. TGFb impairs the degradation of the Sox9 protein
Summary
Glioma is the most common primary central nervous system (CNS) malignant tumor, accounting for about 35–40% of intracranial tumors. Glioma is characterized by high rates of occurrence, invasiveness, and recurrence, with an extremely short overall survival time (OS) and high 5-year mortality rate [1]. While the mechanisms underlying their pathogenesis remain largely elusive, gliomas, especially glioblastomas (GBM), often arise from aberrant differentiation of neural cells [2, 3]. Genetic mutation is known to drive malignant transformation at least in part by “hijacking” neurodevelopmental programs [4, 5]. Increasing evidence has suggested that Sox, an indispensable transcription factor in the development of the nervous system, plays a pivotal role in the pathogenesis of glioma [6,7,8]
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