Downregulation of S100 calcium binding protein A12 inhibits the growth of glioma cells.

BACKGROUND: S100 calcium binding protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified. METHODS: In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of S100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by shRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, colony formation assay, transwell assay,flow cytometry assa and western blot. RESULTS: We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT. CONCLUSION: S100A12 plays a vital role in glioma progression, and may be an important regulatory molecule for biological behaviors of glioma cell lines.

FERMT3 contributes to glioblastoma cell proliferation and chemoresistance to temozolomide through integrin mediated Wnt signaling.

FERMT3, also known as kindlin-3, is one of three kindlin family members expressed in mammals. Kindlins are cytosolic, adaptor proteins that are important activators and regulators of integrin function. They have also been shown to play critical roles in the development and progression of various cancers. In the present study, we hypothesized that FERMT3 would enhance glioblastoma multiforme (GBM) cell survival. Indeed, expression level analyses showed significant FERMT3 upregulation in human glioma tissues as compared to normal brain tissues. The effect was particularly pronounced in high-grade gliomas. We then demonstrated that FERMT3 knockdown suppresses glioma cell proliferation and chemoresistance to temozolomide (TMZ). To determine the mechanism by which FERMT3 enhances glioma cell proliferation and chemoresistance, we examined the effects of FERMT3 on integrin activation and Wnt/ß-catenin signaling. Through the use of western blot assays and TOPflash and FOPflash plasmid transfection into glioma cells lines, we demonstrated that FERMT3 regulates glioma cell activity through integrin-mediated Wnt/ß-catenin signaling. These results suggest that FERMT3 activates integrin activity in high-grade gliomas to enhance glioma cell survival and chemoresistance. The present study thus indicates a potential role for FERMT3 as a genetic target in the treatment of GBM.