Prognostic evaluation of glycogen synthase kinase 3A (GSK3A) mRNA expression in colon cancer patients
Vol 8, Issue 2, 2024
VIEWS - 315 (Abstract) 124 (PDF)
Abstract
Introduction: GSK3, a multifunctional serine/threonine kinase regulates cell-cycle progression, differentiation and apoptosis and its inhibition can have a tumor suppressor/promoter effect, depending on the cell type. There are conflicting reports of GSK3 in cell growth, but most studies have focused on GSK3β and very few on GSK3α in cancer. GSK3α regulates proliferation of melanoma and pancreatic and colon cancer cells, but the predictive role of GSK3A is not known in colon cancer. Material and methods: The prognostic role of GSK3A was assessed in colon cancer patients employing Kaplan-Meier plotter (KM plotter) database. Online ROC plotter tool was used to compare the GSK3A gene expression in colorectal cancer patients receiving any form of chemotherapy. Results: Current results show that higher GSK3A mRNA expression is significantly related to poorer Relapse Free Survival (RFS) in colon cancer patients. Assessment of GSK3A mRNA for different clinicopathological features like clinical stages, TP53 mutation, stage T and stage N highlighted the critical prognostic value of GSK3A mRNA in colon cancer. Discussion and conclusion: GSK3A will help to better predict colon cancer prognosis and to develop better treatment strategies for colon cancer patients and will be beneficial in combating the heterogeneity and complexity of colon cancer.
Keywords
Full Text:
PDFReferences
1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68(6): 394-424. doi: 10.3322/caac.21492
2. Woodgett JR. Molecular cloning and expression of glycogen synthase kinase-3/factor A. The EMBO Journal. 1990; 9(8): 2431-2438. doi: 10.1002/j.1460-2075.1990.tb07419.x
3. Welsh GI, Proud CG. Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B. Biochemical Journal. 1993; 294(3): 625-629. doi: 10.1042/bj2940625
4. Cohen P, Frame S. The renaissance of GSK3. Nature Reviews Molecular Cell Biology. 2001; 2(10): 769-776. doi: 10.1038/35096075
5. Duda P, Akula SM, Abrams SL, et al. Targeting GSK3 and Associated Signaling Pathways Involved in Cancer. Cells. 2020; 9(5): 1110. doi: 10.3390/cells9051110
6. Jope RS, Johnson GVW. The glamour and gloom of glycogen synthase kinase-3. Trends in Biochemical Sciences. 2004; 29(2): 95-102. doi: 10.1016/j.tibs.2003.12.004
7. Medina M, Castro A. Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic. Curr Opin Drug Discov Devel. 2008; 11:533-43.
8. Garcea G, Manson M, Neal C, et al. Glycogen Synthase Kinase-3 Beta; A New Target in Pancreatic Cancer? Current Cancer Drug Targets. 2007; 7(3): 209-215. doi: 10.2174/156800907780618266
9. Obligado SH, Ibraghimov-Beskrovnaya O, Zuk A, et al. CDK/GSK-3 inhibitors as therapeutic agents for parenchymal renal diseases. Kidney International. 2008; 73(6): 684-690. doi: 10.1038/sj.ki.5002731
10. Dewhurst S, Maggirwar SB, Schifitto G, et al. Glycogen Synthase Kinase 3 Beta (GSK-3β) as a Therapeutic Target in NeuroAIDS. Journal of Neuroimmune Pharmacology. 2006; 2(1): 93-96. doi: 10.1007/s11481-006-9051-1
11. MacAulay K, Doble BW, Patel S, et al. Glycogen Synthase Kinase 3α-Specific Regulation of Murine Hepatic Glycogen Metabolism. Cell Metabolism. 2007; 6(4): 329-337. doi: 10.1016/j.cmet.2007.08.013
12. Piazza F, Manni S, Tubi LQ, et al. Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death. BMC Cancer. 2010; 10(1). doi: 10.1186/1471-2407-10-526
13. Wilson W, Baldwin AS. Maintenance of Constitutive IκB Kinase Activity by Glycogen Synthase Kinase-3α/β in Pancreatic Cancer. Cancer Research. 2008; 68(19): 8156-8163. doi: 10.1158/0008-5472.can-08-1061
14. Forde JE, Dale TC. Glycogen synthase kinase 3: A key regulator of cellular fate. Cellular and Molecular Life Sciences. 2007; 64(15): 1930-1944. doi: 10.1007/s00018-007-7045-7
15. Liang MH, Chuang DM. Differential Roles of Glycogen Synthase Kinase-3 Isoforms in the Regulation of Transcriptional Activation. Journal of Biological Chemistry. 2006; 281(41): 30479-30484. doi: 10.1074/jbc.m607468200
16. Hoeflich KP, Luo J, Rubie EA, et al. Requirement for glycogen synthase kinase-3β in cell survival and NF-κB activation. Nature. 2000; 406(6791): 86-90. doi: 10.1038/35017574
17. Borden BA, Baca Y, Xiu J, et al. The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer. Molecular Cancer Therapeutics. 2021; 20(1): 183-190. doi: 10.1158/1535-7163.mct-20-0497
18. Grassilli E, Ianzano L, Bonomo S, et al. GSK3A Is Redundant with GSK3B in Modulating Drug Resistance and Chemotherapy-Induced Necroptosis. Condorelli G, ed. PLoS ONE. 2014; 9(7): e100947. doi: 10.1371/journal.pone.0100947
19. Gao L, Lu Y, Chen HN, et al. Deciphering the Clinical Significance and Kinase Functions of GSK3α in Colon Cancer by Proteomics and Phosphoproteomics. Molecular & Cellular Proteomics. 2023; 22(5): 100545. doi: 10.1016/j.mcpro.2023.100545
20. Guil-Luna S, Rivas-Crespo A, Navarrete-Sirvent C, et al. Clinical significance of glycogen synthase kinase 3 (GSK-3) expression and tumor budding grade in colorectal cancer: Implications for targeted therapy. Biomedicine & Pharmacotherapy. 2023; 167: 115592. doi: 10.1016/j.biopha.2023.115592
21. Cao X, Wu W, Wang D, et al. Glycogen synthase kinase GSK3α promotes tumorigenesis by activating HIF1/VEGFA signaling pathway in NSCLC tumor. Cell Communication and Signaling. 2022; 20(1). doi: 10.1186/s12964-022-00825-3
22. Kaur J. Prognostic Effect of Glycogen Synthase Kinase 3A (GSK3A) mRNA Expression in Breast Cancer Patients. American Journal of Biomedical Sciences. Published online April 2022: 58-71. doi: 10.5099/aj220200058
23. Kovács SA, Fekete JT, Győrffy B. Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors. Acta Pharmacologica Sinica. 2023; 44(9): 1879-1889. doi: 10.1038/s41401-023-01079-6
24. Győrffy B. Discovery and ranking of the most robust prognostic biomarkers in serous ovarian cancer. GeroScience. 2023; 45(3): 1889-1898. doi: 10.1007/s11357-023-00742-4
25. Liu H. Microarray probes and probe sets. Frontiers in Bioscience. 2010; E2(1): 325-338. doi: 10.2741/e93
26. Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA: A Cancer Journal for Clinicians. 2020; 70(3): 145-164. doi: 10.3322/caac.21601
27. Ansa B, Coughlin S, Alema-Mensah E, et al. Evaluation of Colorectal Cancer Incidence Trends in the United States (2000–2014). Journal of Clinical Medicine. 2018; 7(2): 22. doi: 10.3390/jcm7020022
28. Ali A, Hoeflich KP, Woodgett JR. Glycogen Synthase Kinase-3: Properties, Functions, and Regulation. Chemical Reviews. 2001; 101(8): 2527-2540. doi: 10.1021/cr000110o
29. Luo J. Glycogen synthase kinase 3β (GSK3β) in tumorigenesis and cancer chemotherapy. Cancer Letters. 2009; 273(2): 194-200. doi: 10.1016/j.canlet.2008.05.045
30. McCubrey JA, Davis NM, Abrams SL, et al. Diverse roles of GSK-3: Tumor promoter–tumor suppressor, target in cancer therapy. Advances in Biological Regulation. 2014; 54: 176-196. doi: 10.1016/j.jbior.2013.09.013
31. McCubrey JA, Fitzgerald TL, Yang LV, et al. Roles of GSK-3 and microRNAs on epithelial mesenchymal transition and cancer stem cells. Oncotarget. 2016; 8(8): 14221-14250. doi: 10.18632/oncotarget.13991
32. Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multi-tasking kinase. Journal of Cell Science. 2003; 116(7): 1175-1186. doi: 10.1242/jcs.00384
33. Vidri RJ, Fitzgerald TL. GSK-3: An important kinase in colon and pancreatic cancers. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2020; 1867(4): 118626. doi: 10.1016/j.bbamcr.2019.118626
34. Valvezan AJ, Zhang F, Diehl JA, et al. Adenomatous Polyposis Coli (APC) Regulates Multiple Signaling Pathways by Enhancing Glycogen Synthase Kinase-3 (GSK-3) Activity. Journal of Biological Chemistry. 2012; 287(6): 3823-3832. doi: 10.1074/jbc.m111.323337
35. Shakoori A, Ougolkov A, Yu ZW, et al. Deregulated GSK3β activity in colorectal cancer: Its association with tumor cell survival and proliferation. Biochemical and Biophysical Research Communications. 2005; 334(4): 1365-1373. doi: 10.1016/j.bbrc.2005.07.041
36. Ougolkov AV, Fernandez-Zapico ME, Bilim VN, et al. Aberrant Nuclear Accumulation of Glycogen Synthase Kinase-3β in Human Pancreatic Cancer: Association with Kinase Activity and Tumor Dedifferentiation. Clinical Cancer Research. 2006; 12(17): 5074-5081. doi: 10.1158/1078-0432.ccr-06-0196
37. Ougolkov AV, Bone ND, Fernandez-Zapico ME, et al. Inhibition of glycogen synthase kinase-3 activity leads to epigenetic silencing of nuclear factor κB target genes and induction of apoptosis in chronic lymphocytic leukemia B cells. Blood. 2007; 110(2): 735-742. doi: 10.1182/blood-2006-12-060947
38. Kunnimalaiyaan M, Vaccaro AM, Ndiaye MA, et al. Inactivation of glycogen synthase kinase-3β, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells. Molecular Cancer Therapeutics. 2007; 6(3): 1151-1158. doi: 10.1158/1535-7163.mct-06-0665
39. Adler JT, Cook M, Luo Y, et al. Tautomycetin and tautomycin suppress the growth of medullary thyroid cancer cells via inhibition of glycogen synthase kinase-3β. Molecular Cancer Therapeutics. 2009; 8(4): 914-920. doi: 10.1158/1535-7163.mct-08-0712
40. Carter YM, Kunnimalaiyaan S, Chen H, et al. Specific glycogen synthase kinase-3 inhibition reduces neuroendocrine markers and suppresses neuroblastoma cell growth. Cancer Biology & Therapy. 2014; 15(5): 510-515. doi: 10.4161/cbt.28015
41. Ougolkov AV, Fernandez-Zapico ME, Savoy DN, et al. Glycogen Synthase Kinase-3β Participates in Nuclear Factor κB–Mediated Gene Transcription and Cell Survival in Pancreatic Cancer Cells. Cancer Research. 2005; 65(6): 2076-2081. doi: 10.1158/0008-5472.can-04-3642
42. Kunnimalaiyaan S, Clark Gamblin T, Kunnimalaiyaan M. Glycogen synthase kinase-3 inhibitor AR-A014418 suppresses pancreatic cancer cell growth via inhibition of GSK-3-mediated Notch1 expression. HPB. 2015; 17(9): 770-776. doi: 10.1111/hpb.12442
43. Thapa R, Gupta G, Bhat AA, et al. A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies. International Journal of Biological Macromolecules. 2023; 253: 127375. doi: 10.1016/j.ijbiomac.2023.127375
44. Sahin I, Eturi A, De Souza A, et al. Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses. Cancer Biology & Therapy. 2019; 20(8): 1047-1056. doi: 10.1080/15384047.2019.1595283
45. Augello G, Emma MR, Cusimano A, et al. The Role of GSK-3 in Cancer Immunotherapy: GSK-3 Inhibitors as a New Frontier in Cancer Treatment. Cells. 2020; 9(6): 1427. doi: 10.3390/cells9061427
46. Walz A, Ugolkov A, Chandra S, et al. Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer. Clinical Cancer Research. 2017; 23(8): 1891-1897. doi: 10.1158/1078-0432.ccr-15-2240
47. Madhunapantula SV, Sharma A, Gowda R, et al. Identification of glycogen synthase kinase 3α as a therapeutic target in melanoma. Pigment Cell & Melanoma Research. 2013; 26(6): 886-899. doi: 10.1111/pcmr.12156
48. Sharma A, Sharma AK, Madhunapantula SV, et al. Targeting Akt3 Signaling in Malignant Melanoma Using Isoselenocyanates. Clinical Cancer Research. 2009; 15(5): 1674-1685. doi: 10.1158/1078-0432.ccr-08-2214
49. Nakayama M, Oshima M. Mutant p53 in colon cancer. Journal of Molecular Cell Biology. 2018; 11(4): 267-276. doi: 10.1093/jmcb/mjy075
50. Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nature Reviews Cancer. 2007; 7(4): 295-308. doi: 10.1038/nrc2109
51. Dinu D, Dobre M, Panaitescu E. et al. Prognostic significance of KRAS gene mutations in colorectal cancer--preliminary study. J Med Life. 2014; 7: 581-7.
52. Caputo F, Santini C, Bardasi C, et al. BRAF-Mutated Colorectal Cancer: Clinical and Molecular Insights. International Journal of Molecular Sciences. 2019; 20(21): 5369. doi: 10.3390/ijms20215369
53. Tejpar S, Bertagnolli M, Bosman F, et al. Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery. The Oncologist. 2010; 15(4): 390-404. doi: 10.1634/theoncologist.2009-0233
54. Neumann JHL, Jung A, Kirchner T. Molekulare Pathologie des kolorektalen Karzinoms. Der Pathologe. 2015; 36(2): 137-144. doi: 10.1007/s00292-015-0005-3
55. Zeinalian M, Hashemzadeh-Chaleshtori M, Salehi R, Emami MH. Clinical Aspects of Microsatellite Instability Testing in Colorectal Cancer. Adv Biomed Res. 2018; 7:28. doi: 10.4103/abr.abr_185_16.
56. Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer. Nature Medicine. 2015; 21(11): 1350-1356. doi: 10.1038/nm.3967
57. Peng Z, Ji Z, Mei F, et al. Lithium Inhibits Tumorigenic Potential of PDA Cells through Targeting Hedgehog-GLI Signaling Pathway. Xie J, ed. PLoS ONE. 2013; 8(4): e61457. doi: 10.1371/journal.pone.0061457
58. Acikgoz E, Güler G, Camlar M, et al. Glycogen synthase kinase-3 inhibition in glioblastoma multiforme cells induces apoptosis, cell cycle arrest and changing biomolecular structure. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2019; 209: 150-164. doi: 10.1016/j.saa.2018.10.036
59. Park R, Coveler AL, Cavalcante L, et al. GSK-3β in Pancreatic Cancer: Spotlight on 9-ING-41, Its Therapeutic Potential and Immune Modulatory Properties. Biology. 2021; 10(7): 610. doi: 10.3390/biology10070610
60. Schrecengost RS, Green CL, Zhuang Y, et al. In Vitro and In Vivo Antitumor and Anti-Inflammatory Capabilities of the Novel GSK3 and CDK9 Inhibitor ABC1183. Journal of Pharmacology and Experimental Therapeutics. 2018; 365(1): 107-116. doi: 10.1124/jpet.117.245738
DOI: https://doi.org/10.24294/ti.v8.i2.6804
Refbacks
- There are currently no refbacks.
Copyright (c) 2024 Neha Sylvia Walter, Jasmeet Kaur
License URL: https://creativecommons.org/licenses/by/4.0/
This site is licensed under a Creative Commons Attribution 4.0 International License.