Abstract 348P
Background
Glioblastoma (GBM) is one of the most common malignant intracranial tumors exhibiting highly aggressive and invasive features. Sorcin (SRI) is a soluble calcium (Ca2+)-binding protein, one prominent member of penta-EF-hand (PEF) protein family, and was involved in the tumorigenesis. In this study, the expression of SRI and the functional role in the progression of GBM were investigated.
Methods
The expression of SRI in GBM was examined in Oncomine and TCGA database and was further measured in clinical tissues and cell lines by immunohistochemical staining, western blot, and RT-PCR. The biological functions of SRI in GBM were performed in vitro models and the underlying molecular mechanisms were further investigated.
Results
We found that SRI expression was up-regulated in GBM tissues and cells compared to nontumorous samples. The results in vitro demonstrated that tumor proliferation is facilitated by the upregulation of SRI. Concurrently, the migration and invasion of GBM cells were significantly enhanced. Reversely, knocking down of SRI expression attenuated the pro-GBM activities. We further indicated that the overexpression of SRI promoted the epithelial-mesenchymal transformation (EMT) and significantly triggered the PI3K/AKT/mTOR pathway in GBM cells, which was hindered by depletion of SRI. Moreover, the key variant of SRI with a mutation at the number of 159 amino acid was identified and played a crucial role in promoting the oncogenic behaviors induced by SRI overexpression.
Conclusions
Collectively, these findings suggest that SRI was up-regulated in GBM and functions as an oncogenic role in the progression of GBM via triggering the PI3K/AKT/mTOR pathway. Then it highlights that SRI may represent a valuable therapeutic target for the clinical intervention of GBM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Natural Sciences Foundation of China.
Disclosure
All authors have declared no conflicts of interest.