{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:47:00Z","timestamp":1790218020218,"version":"4.1.0"},"reference-count":90,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008501","name":"East Carolina University","doi-asserted-by":"publisher","award":["111110-668715-0000"],"award-info":[{"award-number":["111110-668715-0000"]}],"id":[{"id":"10.13039\/100008501","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glycogen synthase kinase-3 (GSK-3) is a regulator of signaling pathways. KRas is frequently mutated in pancreatic cancers. The growth of certain pancreatic cancers is KRas-dependent and can be suppressed by GSK-3 inhibitors, documenting a link between KRas and GSK-3. To further elucidate the roles of GSK-3\u03b2 in drug-resistance, we transfected KRas-dependent MIA-PaCa-2 pancreatic cells with wild-type (WT) and kinase-dead (KD) forms of GSK-3\u03b2. Transfection of MIA-PaCa-2 cells with WT-GSK-3\u03b2 increased their resistance to various chemotherapeutic drugs and certain small molecule inhibitors. Transfection of cells with KD-GSK-3\u03b2 often increased therapeutic sensitivity. An exception was observed with cells transfected with WT-GSK-3\u03b2 and sensitivity to the BCL2\/BCLXL ABT737 inhibitor. WT-GSK-3\u03b2 reduced glycolytic capacity of the cells but did not affect the basal glycolysis and mitochondrial respiration. KD-GSK-3\u03b2 decreased both basal glycolysis and glycolytic capacity and reduced mitochondrial respiration in MIA-PaCa-2 cells. As a comparison, the effects of GSK-3 on MCF-7 breast cancer cells, which have mutant PIK3CA, were examined. KD-GSK-3\u03b2 increased the resistance of MCF-7 cells to chemotherapeutic drugs and certain signal transduction inhibitors. Thus, altering the levels of GSK-3\u03b2 can have dramatic effects on sensitivity to drugs and signal transduction inhibitors which may be influenced by the background of the tumor.<\/jats:p>","DOI":"10.3390\/cells10040816","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T06:05:43Z","timestamp":1617689143000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["GSK-3\u03b2 Can Regulate the Sensitivity of MIA-PaCa-2 Pancreatic and MCF-7 Breast Cancer Cells to Chemotherapeutic Drugs, Targeted Therapeutics and Nutraceuticals"],"prefix":"10.3390","volume":"10","author":[{"given":"Stephen L.","family":"Abrams","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaw M.","family":"Akula","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2802-9599","authenticated-orcid":false,"given":"Akshaya K.","family":"Meher","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda S.","family":"Steelman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-0270","authenticated-orcid":false,"given":"Agnieszka","family":"Gizak","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Neurobiology, University of Wroc\u0142aw, 50-335 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-4157","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Duda","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Neurobiology, University of Wroc\u0142aw, 50-335 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3511-0459","authenticated-orcid":false,"given":"Dariusz","family":"Rakus","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Neurobiology, University of Wroc\u0142aw, 50-335 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-7260","authenticated-orcid":false,"given":"Alberto M.","family":"Martelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-5345","authenticated-orcid":false,"given":"Stefano","family":"Ratti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9206-8277","authenticated-orcid":false,"given":"Lucio","family":"Cocco","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, Universit\u00e0 di Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Montalto","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Maternal and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, Italy"},{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4923-7220","authenticated-orcid":false,"given":"Melchiorre","family":"Cervello","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, National Research Council (CNR), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ruvolo","sequence":"additional","affiliation":[{"name":"Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7232-7737","authenticated-orcid":false,"given":"Massimo","family":"Libra","sequence":"additional","affiliation":[{"name":"Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, 95123 Catania, Italy"},{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-6826","authenticated-orcid":false,"given":"Luca","family":"Falzone","sequence":"additional","affiliation":[{"name":"Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, 95123 Catania, Italy"},{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Candido","sequence":"additional","affiliation":[{"name":"Research Center for Prevention, Diagnosis and Treatment of Cancer (PreDiCT), University of Catania, 95123 Catania, Italy"},{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-3156","authenticated-orcid":false,"given":"James A.","family":"McCubrey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Brody Building 5N98C, Greenville, NC 27858, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1111\/j.1432-1033.1980.tb06059.x","article-title":"Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase","volume":"107","author":"Embi","year":"1980","journal-title":"Eur. J. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1002\/j.1460-2075.1990.tb07419.x","article-title":"Molecular cloning and expression of glycogen synthase kinase-3\/factor A","volume":"9","author":"Woodgett","year":"1990","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Duda, P., Akula, S.M., Abrams, S.L., Steelman, L.S., Martelli, A.M., Cocco, L., Ratti, S., Candido, S., Libra, M., and Montalto, G. (2020). Targeting GSK3 and associated signaling pathways involved in cancer. Cells, 9.","DOI":"10.3390\/cells9051110"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"118770","DOI":"10.1016\/j.bbamcr.2020.118770","article-title":"GSK-3 and miRs: Master regulators of therapeutic sensitivity of cancer cells","volume":"1867","author":"Duda","year":"2020","journal-title":"Biochim. Biophy. Acta Mol. Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11960","DOI":"10.1073\/pnas.220413597","article-title":"Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A","volume":"97","author":"Fang","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/378785a0","article-title":"Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B","volume":"378","author":"Cross","year":"1995","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1042\/bj3030701","article-title":"Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation","volume":"303","author":"Stambolic","year":"1994","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1042\/bj2960015","article-title":"Inactivation of glycogen synthase kinase-3 beta by phosphorylation: New kinase connections in insulin and growth-factor signalling","volume":"296","author":"Sutherland","year":"1993","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.2174\/1389450110607011377","article-title":"Glycogen synthase kinase-3--an overview of an over-achieving protein kinase","volume":"7","author":"Kockeritz","year":"2006","journal-title":"Curr. Drug Targets"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/leu.2013.184","article-title":"Multifaceted roles of GSK-3 and Wnt\/\u03b2-catenin in hematopoiesis and leukemogenesis: Opportunities for therapeutic intervention","volume":"28","author":"McCubrey","year":"2014","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1016\/j.bbamcr.2016.09.004","article-title":"Effects of mutations in Wnt\/\u03b2-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer","volume":"1863","author":"McCubrey","year":"2016","journal-title":"Biochim Biophy. Acta Mol. Cell Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14221","DOI":"10.18632\/oncotarget.13991","article-title":"Roles of GSK-3 and microRNAs on epithelial mesenchymal transition and cancer stem cells","volume":"8","author":"McCubrey","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.18632\/oncotarget.240","article-title":"Ras\/Raf\/MEK\/ERK and PI3K\/PTEN\/Akt\/mTOR inhibitors: Rationale and importance to inhibiting these pathways in human health","volume":"2","author":"Chappell","year":"2011","journal-title":"Oncotarget"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/leu.2011.46","article-title":"Targeting the translational apparatus to improve leukemia therapy: Roles of the PI3K\/PTEN\/Akt\/mTOR pathway","volume":"25","author":"Martelli","year":"2011","journal-title":"Leukemia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"192","DOI":"10.18632\/aging.100296","article-title":"Roles of the Raf\/MEK\/ERK and PI3K\/PTEN\/Akt\/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging","volume":"3","author":"Steelman","year":"2011","journal-title":"Aging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.18632\/oncotarget.659","article-title":"Ras\/Raf\/MEK\/ERK and PI3K\/PTEN\/Akt\/mTOR Cascade Inhibitors: How mutations can result in therapy resistance and how to overcome resistance","volume":"3","author":"McCubrey","year":"2012","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E1204","DOI":"10.1073\/pnas.1110195108","article-title":"Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation","volume":"108","author":"Shin","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.4161\/cc.11.6.19784","article-title":"Glycogen synthase kinase (GSK)-3 and mammalian target of rapamycin complex 1 (mTORC1) cooperate to regulate protein S6 kinase 1 (S6K1)","volume":"11","author":"Shin","year":"2012","journal-title":"Cell Cycle"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5217","DOI":"10.4049\/jimmunol.1002513","article-title":"Convergence of the mammalian target of rapamycin complex 1- and glycogen synthase kinase 3-\u03b2-signaling pathways regulates the innate inflammatory response","volume":"186","author":"Wang","year":"2011","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1038\/onc.2013.113","article-title":"Glycogen synthase kinase-3\u03b2 positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1","volume":"33","author":"Shin","year":"2014","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11010-010-0544-0","article-title":"Regulation of GSK3 isoforms by phosphatases PP1 and PP2A","volume":"344","author":"Langa","year":"2010","journal-title":"Mol. Cell. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"954","DOI":"10.18632\/oncotarget.652","article-title":"Mutations and deregulation of Ras\/Raf\/MEK\/ERK and PI3K\/PTEN\/Akt\/mTOR cascades which alter therapy response","volume":"3","author":"McCubrey","year":"2012","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jbior.2015.06.003","article-title":"Roles of EGFR and KRAS and their downstream signaling pathways in pancreatic cancer and pancreatic cancer stem cells","volume":"59","author":"Fitzgerald","year":"2015","journal-title":"Adv. Biol. Regul."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"a031435","DOI":"10.1101\/cshperspect.a031435","article-title":"KRAS: The critical driver and therapeutic target for pancreatic cancer","volume":"8","author":"Waters","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/IGC.0b013e31820d7366","article-title":"Overexpression of glycogen synthase kinase-3 in ovarian carcinoma cells with acquired paclitaxel resistance","volume":"21","author":"Fu","year":"2011","journal-title":"Int. J. Gynecolog. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.bbrc.2012.05.147","article-title":"GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC)","volume":"42","author":"Kawazoe","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1002\/ijc.25949","article-title":"Anticancer efficacy of deguelin in human prostate cancer cells targeting glycogen synthase kinase-3 beta\/beta-catenin pathway","volume":"129","author":"Thamilselvan","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.canlet.2008.05.045","article-title":"Glycogen synthase kinase 3beta (GSK3beta) in tumorigenesis and cancer chemotherapy","volume":"273","author":"Luo","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.bbrc.2005.07.041","article-title":"Deregulated GSK3beta activity in colorectal cancer: Its association with tumor cell survival and proliferation","volume":"334","author":"Shakoori","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2217\/14796694.2.1.91","article-title":"Targeting GSK-3: A promising approach for cancer therapy?","volume":"2","author":"Ougolkov","year":"2006","journal-title":"Future Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.canlet.2011.10.033","article-title":"ShRNA silencing glycogen synthase kinase-3 beta inhibits tumor growth and angiogenesis in pancreatic cancer","volume":"316","author":"Zhou","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_32","first-page":"95","article-title":"Mutant K-RAS promotes invasion and metastasis in pancreatic cancer through GTPase signaling pathways","volume":"8","author":"Padavano","year":"2015","journal-title":"Cancer Growth Metastasis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.18632\/oncotarget.2037","article-title":"GSK-3 as potential target for therapeutic intervention in cancer","volume":"5","author":"McCubrey","year":"2014","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7756","DOI":"10.1158\/0008-5472.CAN-06-4665","article-title":"The role of glycogen synthase kinase 3beta in the transformation of epidermal cells","volume":"67","author":"Ma","year":"2007","journal-title":"Cancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.mito.2013.11.003","article-title":"Glycogen synthase kinase-3 (GSK3) controls deoxyglucose-induced mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells","volume":"14","author":"Ngamsiri","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1158\/1078-0432.CCR-06-0196","article-title":"Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: Association with kinase activity and tumor dedifferentiation","volume":"12","author":"Ougolkov","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"820","DOI":"10.4161\/cc.27728","article-title":"Inhibition of GSK-3\u03b2 activity can result in drug and hormonal resistance and alter sensitivity to targeted therapy in MCF-7 breast cancer cells","volume":"13","author":"Sokolosky","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1083\/jcb.200409067","article-title":"Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: Implications for the epithelial-mesenchymal transition","volume":"168","author":"Bachelder","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11462","DOI":"10.1158\/0008-5472.CAN-06-1969","article-title":"Adiponectin modulates the glycogen synthase kinase-3beta\/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice","volume":"66","author":"Wang","year":"2006","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14740\/wjon1166","article-title":"Epidemiology of pancreatic cancer: Global trends, etiology and risk factors","volume":"10","author":"Rawla","year":"2019","journal-title":"World J. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.pan.2014.10.001","article-title":"Addressing the challenges of pancreatic cancer: Future directions for improving outcomes","volume":"5","author":"Hidalgo","year":"2015","journal-title":"Pancreatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jbior.2014.05.001","article-title":"Pancreatic cancer stem cells: Association with cell surface markers, prognosis, resistance, metastasis and treatment","volume":"56","author":"Fitzgerald","year":"2014","journal-title":"Adv. Biol. Reg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1073\/pnas.0908428107","article-title":"Mutant p53 drives metastasis and overcomes growth arrest\/senescence in pancreatic cancer","volume":"107","author":"Morton","year":"2010","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1158\/2159-8290.CD-12-0541","article-title":"GSK-3\u03b1 promotes oncogenic KRAS function in pancreatic cancer via TAK1-TAB stabilization and regulation of noncanonical NF-\u03baB","volume":"3","author":"Bang","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.4161\/cc.24739","article-title":"p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells","volume":"12","author":"Kim","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1158\/0008-5472.CAN-04-3642","article-title":"Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells","volume":"65","author":"Ougolkov","year":"2005","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5154","DOI":"10.1038\/s41467-018-07644-6","article-title":"GSK3 suppression upregulates \u03b2-catenin and c-Myc to abrogate KRas-dependent tumors","volume":"9","author":"Kazi","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/MPA.0b013e3181c15963","article-title":"Phenotype and genotype of pancreatic cancer cell lines","volume":"39","author":"Deer","year":"2010","journal-title":"Pancreas"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100633","DOI":"10.1016\/j.jbior.2019.04.003","article-title":"Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells","volume":"73","author":"Akula","year":"2019","journal-title":"Adv. Biol. Regul."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/jnci\/51.5.1409","article-title":"A human cell line from a pleural effusion derived from a breast carcinoma","volume":"51","author":"Soule","year":"1973","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/374617a0","article-title":"Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos","volume":"374","author":"He","year":"1995","journal-title":"Nature"},{"key":"ref_52","first-page":"980","article-title":"Improved retroviral vectors for gene transfer and expression","volume":"7","author":"Miller","year":"1989","journal-title":"Biotechniques"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/978-1-4939-9027-6_18","article-title":"Using Seahorse machine to measure OCR and ECAR in cancer cells","volume":"Volume 128","author":"Zhang","year":"2019","journal-title":"Methods in Molecular Biology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1080\/14728222.2020.1743681","article-title":"Glycogen synthase kinase-3\u03b2: A novel therapeutic target for pancreatic cancer","volume":"24","author":"Ding","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/path.4928","article-title":"Glycogen synthase kinase-3\u03b2 ablation limits pancreatitis-induced acinar-to-ductal metaplasia","volume":"243","author":"Ding","year":"2017","journal-title":"J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.1038\/onc.2011.90","article-title":"Mutant K-Ras increases GSK-3\u03b2 gene expression via an ETS-p300 transcriptional complex in pancreatic cancer","volume":"34","author":"Zhang","year":"2011","journal-title":"Oncogene"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1476-4598-12-86","article-title":"The complexity of NF-\u03baB signaling in inflammation and cancer","volume":"12","author":"Hoesel","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.ccell.2018.10.001","article-title":"KRAS suppression-induced degradation of MYC is antagonized by a MEK5-ERK5 compensatory mechanism","volume":"34","author":"Vaseva","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ccell.2020.05.010","article-title":"Altered RNA splicing by mutant p53 activates oncogenic RAS signaling in pancreatic cancer","volume":"38","author":"Penson","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1158\/1535-7163.MCT-15-0309","article-title":"GSK-3\u03b2 governs inflammation-induced NFATc2 signaling hubs to promote pancreatic cancer progression","volume":"15","author":"Baumgart","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"38553","DOI":"10.1038\/srep38553","article-title":"GSK-3\u03b2 controls NF-kappaB activity via IKK\u03b3\/NEMO","volume":"6","author":"Medunjanin","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/j.1349-7006.2009.01405.x","article-title":"In vitro and in vivo evidence that a combination of lapatinib plus S-1 is a promising treatment for pancreatic cancer","volume":"101","author":"Komoto","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1158\/0008-5472.SABCS-2150","article-title":"In vivo activity of ARRY-543, a potent, small molecule inhibitor of EGFR\/ErbB-2 in combination with trastuzumab or docetaxel","volume":"69","author":"Lee","year":"2009","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.cell.2018.01.006","article-title":"Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor","volume":"172","author":"Janes","year":"2018","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e90476","DOI":"10.1371\/journal.pone.0090476","article-title":"Pancreatic satellite cells derived galectin-1 increase the progression and less survival of pancreatic ductal adenocarcinoma","volume":"9","author":"Tang","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1158\/1535-7163.MCT-16-0690","article-title":"A novel galectin-1 inhibitor discovered through one-bead two-compound library potentiates the antitumor effects of paclitaxel in vivo","volume":"16","author":"Shih","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Pav\u00f3n, M.A., Arroyo-Solera, I., C\u00e9spedes, M.V., Casanova, I., Le\u00f3n, X., and Mangues, R. (2016). uPA\/uPAR and SERPINE1 in head and neck cancer: Role in tumor resistance, metastasis, prognosis and therapy. Oncotarget, 57351\u201357366.","DOI":"10.18632\/oncotarget.10344"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.18632\/aging.102776","article-title":"TP53\/miR-34a-associated signaling targets SERPINE1 expression in human pancreatic cancer","volume":"12","author":"Akula","year":"2020","journal-title":"Aging"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Seker, F., Cingoz, A., Sur-Erdem, \u0130., Erguder, N., Erkent, A., Uyulur, F., Esai Selvan, M., G\u00fcm\u00fc\u015f, Z.H., G\u00f6nen, M., and Bayraktar, H. (2019). Identification of SERPINE1 as a regulator of glioblastoma cell dispersal with transcriptome profiling. Cancers, 11.","DOI":"10.3390\/cancers11111651"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"353","DOI":"10.7555\/JBR.30.20150107","article-title":"Deciphering the role of hedgehog signaling in pancreatic cancer","volume":"30","author":"Gu","year":"2016","journal-title":"J. Biomed. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41416-019-0683-3","article-title":"Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma","volume":"122","author":"Sugar","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"van Mackelenbergh, M.G., Stroes, C.I., Spijker, R., van Eijck, C., Wilmink, J.W., Bijlsma, M.F., and van Laarhoven, H. (2019). Clinical trials targeting the stroma in pancreatic cancer: A systematic review and meta-analysis. Cancers, 11.","DOI":"10.3390\/cancers11050588"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12943-019-1090-3","article-title":"AXL receptor tyrosine kinase as a promising anti-cancer approach: Functions, molecular mechanisms and clinical applications","volume":"18","author":"Zhu","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.lfs.2018.02.033","article-title":"Axl inhibitors as novel cancer therapeutic agents","volume":"198","author":"Shen","year":"2018","journal-title":"Life Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1055\/s-0035-1558227","article-title":"A systematic review of the anticancer properties of compounds isolated from licorice (Gancao)","volume":"81","author":"Tang","year":"2015","journal-title":"Planta Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3892\/or.2013.2849","article-title":"Combination of liquiritin, isoliquiritin and isoliquirigenin induce apoptotic cell death through upregulating p53 and p21 in the A549 non-small cell lung cancer cells","volume":"31","author":"Zhou","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.3389\/fphar.2018.01455","article-title":"Isoliquiritin apioside suppresses in vitro invasiveness and angiogenesis of cancer cells and endothelial cells","volume":"9","author":"Kim","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/ni.3664","article-title":"Gsk3 is a metabolic checkpoint regulator in B cells","volume":"18","author":"Jellusova","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1016\/j.yexcr.2012.04.012","article-title":"GSK3 inactivation is involved in mitochondrial complex IV defect in transforming growth factor (TGF) \u03b21-induced senescence","volume":"318","author":"Byun","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fonc.2013.00016","article-title":"GSK-3 and mitochondria in cancer cells","volume":"3","author":"Chiara","year":"2013","journal-title":"Front. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e00382","DOI":"10.1042\/BSR20160174","article-title":"Knockdown of GSK3\u03b2 increases basal autophagy and AMPK signalling in nutrient-laden human aortic endothelial cells","volume":"36","author":"Weikel","year":"2016","journal-title":"Biosci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41591-019-0368-8","article-title":"Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer","volume":"25","author":"Bryant","year":"2019","journal-title":"Nat. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9232","DOI":"10.1128\/JVI.01072-15","article-title":"A screen for extracellular signal-regulated kinase-primed glycogen synthase kinase 3 substrates identifies the p53 i3hibitor iASPP","volume":"89","author":"Woodard","year":"2015","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jbior.2017.05.002","article-title":"Targeting the Akt, GSK-3, Bcl-2 axis in acute myeloid leukemia","volume":"65","author":"Ricciardi","year":"2017","journal-title":"Adv. Biol. Regul."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1158\/0008-5472.CAN-12-1365","article-title":"Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism","volume":"73","author":"Rahmani","year":"2013","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19977","DOI":"10.1038\/s41598-019-56461-4","article-title":"ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutic.s in bladder cancer","volume":"9","author":"Kuroki","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jbior.2018.02.002","article-title":"Metformin influences drug sensitivity in pancreatic cancer cells","volume":"68","author":"Candido","year":"2018","journal-title":"Adv. Biol. Regul."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.canlet.2016.07.006","article-title":"GSK-3 inhibition overcomes chemoresistance in human breast cancer","volume":"380","author":"Ugolkov","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1089\/omi.2017.0020","article-title":"NF-\u03baB is a potential molecular drug target in triple-negative breast cancers","volume":"21","author":"Poma","year":"2017","journal-title":"OMICS"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13058-019-1125-0","article-title":"GSK3\u03b2 regulates epithelial-mesenchymal transition and cancer stem cell properties in triple-negative breast cancer","volume":"21","author":"Vijay","year":"2019","journal-title":"Breast Cancer Res."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/4\/816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:20Z","timestamp":1760361980000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/4\/816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":90,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cells10040816"],"URL":"https:\/\/doi.org\/10.3390\/cells10040816","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]}}}