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Inhibiting Bet1-mediated transport of MMP14 to plasma membrane impaired GBM cell invasion

Luo, Y.; Li, J.; Xiong, Y.

2023-02-16 cell biology
10.1101/2023.02.16.525994 bioRxiv
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PurposeGlioblastoma (GBM) is the most aggressive and common form of brain cancer in adults. GBM is characterised by poor survival as the lack of effective therapies. This research aims to detect the roles of SNAREs in GBM and improve our knowledge of targeting therapy for GBM. Materials and methodsthe expression of SNAREs and their correlation with overall survival (OS) in GBM are investigated using the GEPIA. The level of BET1 in GBM cell lines was tested by RT-qPCR, and its biological functions in GBM cells were tested by Transwell assay and CCK8 kit. The effect of BET1 on the location of MMP14 is identified by Immunofluorescence. ResultsThe expression profile of SNARE family members in GBM tissue is changed dramatically. Among them, the mRNA levels of BET1 and VAMP3 are up-regulated, and their expression negatively correlates with OS. BET1 is also increased in GBM Cell Lines, and it is required for efficient GBM cell migration and invasion partly because it mediates the transport of MMP14 to the plasma membrane. ConclusionGBM has highly diffusive and infiltrative ability in nature, making complete surgical resection almost impossible. Our data shows that BET1 is highly expressed in GBM tissue, negatively correlated with OS, and essential for GBM cell migration and invasion. These results indicate that SNARE BET1 may present a potential target for GBM treatment.

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