Antagonistic Role of GSK3 Isoforms in Glioma Survival

Overview

Journal J Cancer

Specialty Oncology

Date 2018 May 29

PMID 29805711

Citations 12

Authors

Vidhi Vashishtha

Nupur Jinghan

Ajay K Yadav

Affiliations

Soon will be listed here.

Abstract

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.

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References

Babic I, Anderson E, Tanaka K, Guo D, Masui K, Li B . EGFR mutation-induced alternative splicing of Max contributes to growth of glycolytic tumors in brain cancer. Cell Metab. 2013; 17(6):1000-1008. PMC: 3679227. DOI: 10.1016/j.cmet.2013.04.013. View

Zong Z, Pang H, Yu R, Jiao Y . PCDH8 inhibits glioma cell proliferation by negatively regulating the AKT/GSK3β/β-catenin signaling pathway. Oncol Lett. 2017; 14(3):3357-3362. PMC: 5588001. DOI: 10.3892/ol.2017.6629. View

Rossig L, Badorff C, Holzmann Y, Zeiher A, Dimmeler S . Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cip1 degradation. J Biol Chem. 2002; 277(12):9684-9. DOI: 10.1074/jbc.M106157200. View

Chabot B, Lebel C, Hutchison S, Nasim F, Simard M . Heterogeneous nuclear ribonucleoprotein particle A/B proteins and the control of alternative splicing of the mammalian heterogeneous nuclear ribonucleoprotein particle A1 pre-mRNA. Prog Mol Subcell Biol. 2002; 31:59-88. DOI: 10.1007/978-3-662-09728-1_3. View

Hetman M, Hsuan S, Habas A, Higgins M, Xia Z . ERK1/2 antagonizes glycogen synthase kinase-3beta-induced apoptosis in cortical neurons. J Biol Chem. 2002; 277(51):49577-84. DOI: 10.1074/jbc.M111227200. View

Zhao P, Li Q, Shi Z, Li C, Wang L, Liu X . GSK-3β regulates tumor growth and angiogenesis in human glioma cells. Oncotarget. 2015; 6(31):31901-15. PMC: 4741649. DOI: 10.18632/oncotarget.5043. View

Sutherland C, Leighton I, Cohen P . Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling. Biochem J. 1993; 296 ( Pt 1):15-9. PMC: 1137648. DOI: 10.1042/bj2960015. View

Li Y, Lu H, Huang Y, Xiao R, Cai X, He S . Glycogen synthase kinases-3beta controls differentiation of malignant glioma cells. Int J Cancer. 2009; 127(6):1271-82. DOI: 10.1002/ijc.25020. View

Oltean S, Bates D . Hallmarks of alternative splicing in cancer. Oncogene. 2013; 33(46):5311-8. DOI: 10.1038/onc.2013.533. View

10.

Dong G, Mao Q, Xia W, Xu Y, Wang J, Xu L . PKM2 and cancer: The function of PKM2 beyond glycolysis. Oncol Lett. 2016; 11(3):1980-1986. PMC: 4774429. DOI: 10.3892/ol.2016.4168. View

11.

Mukherjee J, Phillips J, Zheng S, Wiencke J, Ronen S, Pieper R . Pyruvate kinase M2 expression, but not pyruvate kinase activity, is up-regulated in a grade-specific manner in human glioma. PLoS One. 2013; 8(2):e57610. PMC: 3581484. DOI: 10.1371/journal.pone.0057610. View

12.

Wang Q, Zhou Y, Wang X, Evers B . Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase. Oncogene. 2005; 25(1):43-50. PMC: 1413679. DOI: 10.1038/sj.onc.1209004. View

13.

Dreyfuss G, Kim V, Kataoka N . Messenger-RNA-binding proteins and the messages they carry. Nat Rev Mol Cell Biol. 2002; 3(3):195-205. DOI: 10.1038/nrm760. View

14.

Li B, Thrasher J, Terranova P . Glycogen synthase kinase-3: a potential preventive target for prostate cancer management. Urol Oncol. 2015; 33(11):456-63. PMC: 4753786. DOI: 10.1016/j.urolonc.2015.05.006. View

15.

Rayasam G, Tulasi V, Sodhi R, Davis J, Ray A . Glycogen synthase kinase 3: more than a namesake. Br J Pharmacol. 2009; 156(6):885-98. PMC: 2697722. DOI: 10.1111/j.1476-5381.2008.00085.x. View

16.

Guil S, Caceres J . The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat Struct Mol Biol. 2007; 14(7):591-6. DOI: 10.1038/nsmb1250. View

17.

Kotliarova S, Pastorino S, Kovell L, Kotliarov Y, Song H, Zhang W . Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation. Cancer Res. 2008; 68(16):6643-51. PMC: 2585745. DOI: 10.1158/0008-5472.CAN-08-0850. View

18.

Caunt C, Sale M, Smith P, Cook S . MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road. Nat Rev Cancer. 2015; 15(10):577-92. DOI: 10.1038/nrc4000. View

19.

Cammas A, Pileur F, Bonnal S, Lewis S, Leveque N, Holcik M . Cytoplasmic relocalization of heterogeneous nuclear ribonucleoprotein A1 controls translation initiation of specific mRNAs. Mol Biol Cell. 2007; 18(12):5048-59. PMC: 2096577. DOI: 10.1091/mbc.e07-06-0603. View

20.

Yadav A, Vashishta V, Joshi N, Taneja P . AR-A 014418 Used against GSK3beta Downregulates Expression of hnRNPA1 and SF2/ASF Splicing Factors. J Oncol. 2014; 2014:695325. PMC: 3914408. DOI: 10.1155/2014/695325. View