J Cancer 2018; 9(10):1846-1855. doi:10.7150/jca.21248
Antagonistic role of GSK3 isoforms in glioma survival
Cancer Genetics Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi (North Campus), Delhi- 110007, India
Vashishtha V, Jinghan N, K.Yadav A. Antagonistic role of GSK3 isoforms in glioma survival. J Cancer 2018; 9(10):1846-1855. doi:10.7150/jca.21248. Available from http://www.jcancer.org/v09p1846.htm
GSK3 (Glycogen Synthase Kinase-3) function in brain is contributed by two distinct gene GSK3 alpha and GSK3 beta. Present findings indicate that imbalance in between GSK3 alpha and beta isoform contributes oncogenesis. In gliomas, GSK3 isoform specific functions are different then as reported for melanoma, prostate cancer, lung cancer etc. Both the isoforms of GSK3 are inversely regulating hnRNPA1 (RNA binding protein) expression, subsequently affecting RNA alternative splicing (BIN1, RON, Mcl1, PKM) in gliomas. Elevated expression of c-Myc, hnRNPA1, Phospo-ERK1/2 and Cyclin D1 in GSK3 alpha knock down cells, resembles GSK3 beta isoform overexpressing glioma cells, promotes cell survival. HnRNPA1 dependent survival signaling pathway were elaborated using si RNA approach or by over expressing cloned hnRNPA1 gene in U87 glioma cells. Therefore, performed study empirically support GSK3β inhibition along with restoration of GSK3α would be a good strategy to target gliomas.
Keywords: Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), Alternative splicing, GSK3, Brain Tumor, ERK