Overexpression of FBXO17 Promotes the Proliferation, Migration and Invasion of Glioma Cells Through the Akt/GSK-3β/Snail Pathway

Abstract

FBXO17 is a newly studied F-box protein associated with high-grade glioma. However, its exact role in glioma remains unclear. In the present study, we aimed to investigate the role of FBXO17 in glioma both in vitro and in vivo and explore the underlying mechanism. Our results showed that FBXO17 mRNA and protein levels were upregulated in glioma cells including U87, U251, SHG44, and U-118-MG cells as compared to the HA1800 cells. Downregulation of FBXO17 significantly suppressed the cellular behaviors of glioma cells including cell proliferation, migration, and invasion. In addition, FBXO17 knockdown induced E-cadherin expression and inhibited N-cadherin and vimentin expression at mRNA and protein levels in glioma cells. In contrast, overexpression of FBXO17 promoted cell proliferation, migration, invasion and EMT process. Furthermore, FBXO17 regulated the Akt/GSK-3β/snail signaling pathway in glioma cells with significant changes in the expression levels of p-Akt, p-GSK-3β and snail. Additionally, inhibition of Akt by LY294002 reversed the effects of FBXO17 overexpression on cellular behaviors of glioma cells. Finally, in vivo mouse xenograft assay proved that downregulation of FBXO17 suppresses the tumorigenesis of glioma. In conclusion, these findings demonstrated that FBXO17 acted as a promotor of glioma development via modulating Akt/GSK-3β/snail signaling pathway.

Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis

“…The EMT process and associated loss of epithelial cell phenotypes can be regulated in response to particular extracellular signaling molecules, with cell surface receptors and transcription factors ultimately transducing these signals to alter cellular characteristics ( 26 , 27 ). The PI3K/AKT/GSK3β/Snail signaling has previously been shown to be critical to tumor metastasis via the modulation of EMT induction in multiple cancers ( 28 – 30 ). As such, we herein assessed the ability of ECM1 to affect the migratory and invasive activity of CRC cells via this signaling pathway, revealing that ECM knockdown was associated with decreases in p-AKT, p-GSK3β, and Snail expression in CRC cells, whereas ECM overexpression yielded the opposite outcome.…”

The genes significantly associated with an improved prognosis and long-term survival of glioblastoma

“…Meanwhile, among the 33 independent and significant genes, CHST2, PPCS, and FBXO17 were considered to influence the prognosis of GBM in relation to metabolism [ 23 , 29 , 35 , 36 ]. The role of CHST2 in GBM is largely unknown, however, it is thought to have a negative influence on long-term survival in GBM patients in our study.…”

Non-negative matrix factorization model-based construction for molecular clustering and prognostic assessment of head and neck squamous carcinoma

“…Targeting TNFRSF4 has a role in anti-breast cancer and melanoma treatment [24]. In glioma, hepatocellular carcinoma and lung adenocarcinoma, FBXO17 promotes cell proliferation, migration and invasion through the Akt/GSK-3β/Snail pathway [25,26,27]. Not only is IRF9 important for antiviral responses, it is also involved in autoimmunity [28].…”