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Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.<\/jats:p>","DOI":"10.3390\/ph16050671","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T12:14:08Z","timestamp":1682943248000},"page":"671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The STAT3-Regulated Autophagy Pathway in Glioblastoma"],"prefix":"10.3390","volume":"16","author":[{"given":"Ronald Nicholas","family":"Laribee","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The Center for Cancer Research, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Boucher","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saivikram","family":"Madireddy","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2809-1234","authenticated-orcid":false,"given":"Lawrence M.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The Center for Cancer Research, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1023\/A:1006091608586","article-title":"Brain tumor survival: Results from the National Cancer Data Base","volume":"40","author":"Surawicz","year":"1998","journal-title":"J. Neuro-Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa043331","article-title":"MGMT gene silencing and benefit from temozolomide in glioblastoma","volume":"352","author":"Hegi","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1200\/JCO.1999.17.8.2572","article-title":"Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials","volume":"17","author":"Wong","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s10014-011-0029-1","article-title":"Genetic profile of astrocytic and oligodendroglial gliomas","volume":"28","author":"Ohgaki","year":"2011","journal-title":"Brain Tumor Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/bpa.12018","article-title":"Glioblastoma with oligodendroglioma component (GBM-O): Molecular genetic and clinical characteristics","volume":"23","author":"Appin","year":"2013","journal-title":"Brain Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ccr.2006.02.019","article-title":"Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis","volume":"9","author":"Phillips","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1586\/erm.12.30","article-title":"The cellular origin for malignant glioma and prospects for clinical advancements","volume":"12","author":"Zong","year":"2012","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"22095","DOI":"10.18632\/oncotarget.25188","article-title":"The critical role that STAT3 plays in glioma-initiating cells: STAT3 addiction in glioma","volume":"9","author":"Ganguly","year":"2018","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.semcancer.2021.02.014","article-title":"Cancer cell heterogeneity & plasticity in glioblastoma and brain tumors","volume":"82","author":"Lauko","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ganguly, D., Cai, C., Sims, M.M., Yang, C.H., Thomas, M., Cheng, J., Saad, A.G., and Pfeffer, L.M. (2019). APELA Expression in Glioma, and Its Association with Patient Survival and Tumor Grade. Pharmaceuticals, 12.","DOI":"10.3390\/ph12010045"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nrc3918","article-title":"Heterogeneity of epidermal growth factor receptor signalling networks in glioblastoma","volume":"15","author":"Furnari","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The somatic genomic landscape of glioblastoma","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2008). Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 455, 1061\u20131068.","DOI":"10.1038\/nature07385"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1073\/pnas.89.7.2965","article-title":"Structural alterations of the epidermal growth factor receptor gene in human gliomas","volume":"89","author":"Wong","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11060-006-9220-3","article-title":"Expression of nine tumour antigens in a series of human glioblastoma multiforme: Interest of EGFRvIII, IL-13Ralpha2, gp100 and TRP-2 for immunotherapy","volume":"81","author":"Saikali","year":"2007","journal-title":"J. Neuro-Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6767","DOI":"10.1158\/1078-0432.CCR-05-0722","article-title":"Food and Drug Administration Drug approval summary: Temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme","volume":"11","author":"Cohen","year":"2005","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1093\/neuonc\/nos153","article-title":"A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme","volume":"14","author":"Ronning","year":"2012","journal-title":"Neuro-Oncology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1200\/JCO.2002.20.5.1375","article-title":"Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide","volume":"20","author":"Stupp","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1517\/14656566.8.18.3133","article-title":"Management of glioblastoma","volume":"8","author":"Aoki","year":"2007","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Rajaratnam, V., Islam, M.M., Yang, M., Slaby, R., Ramirez, H.M., and Mirza, S.P. (2020). Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments. Cancers, 12.","DOI":"10.3390\/cancers12040937"},{"key":"ref_25","first-page":"121","article-title":"Current trends in the surgical management and treatment of adult glioblastoma","volume":"3","author":"Young","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.bbrc.2017.06.111","article-title":"Unphosphorylated STAT3 regulates the antiproliferative, antiviral, and gene-inducing actions of type I interferons","volume":"490","author":"Pfeffer","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.bbrc.2017.07.098","article-title":"The effects of type I interferon on glioblastoma cancer stem cells","volume":"491","author":"Du","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39172","DOI":"10.1074\/jbc.M111.285098","article-title":"MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells","volume":"286","author":"Yang","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8108","DOI":"10.1158\/0008-5472.CAN-10-2579","article-title":"IFN induces miR-21 through a signal transducer and activator of transcription 3-dependent pathway as a suppressive negative feedback on IFN-induced apoptosis","volume":"70","author":"Yang","year":"2010","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"986","DOI":"10.4049\/jimmunol.178.2.986","article-title":"Identification of CXCL11 as a STAT3-dependent gene induced by IFN","volume":"178","author":"Yang","year":"2007","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25849","DOI":"10.1074\/jbc.M413721200","article-title":"Interferon alpha activates NF-kappaB in JAK1-deficient cells through a TYK2-dependent pathway","volume":"280","author":"Yang","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5568","DOI":"10.1073\/pnas.95.10.5568","article-title":"STAT3 complements defects in an interferon-resistant cell line: Evidence for an essential role for STAT3 in interferon signaling and biological activities","volume":"95","author":"Yang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1126\/science.276.5317.1418","article-title":"STAT3 as an adapter to couple phosphatidylinositol-3-kinase to the IFNAR-1 chain of the type I IFN receptor","volume":"276","author":"Pfeffer","year":"1997","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8057","DOI":"10.1074\/jbc.271.14.8057","article-title":"Direct association of STAT3 with the IFNAR1 signal transducing chain of the type I IFN receptor","volume":"271","author":"Yang","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0092-8674(94)90235-6","article-title":"Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway","volume":"77","author":"Akira","year":"1994","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1126\/science.8140422","article-title":"Stat3: A STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6","volume":"264","author":"Zhong","year":"1994","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6613","DOI":"10.1038\/sj.onc.1204086","article-title":"STAT proteins: Novel molecular targets for cancer drug discovery","volume":"19","author":"Turkson","year":"2000","journal-title":"Oncogene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1038\/sj.onc.1203527","article-title":"STATs in oncogenesis","volume":"19","author":"Bowman","year":"2000","journal-title":"Oncogene"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Garner, J.M., Ellison, D.W., Finkelstein, D., Ganguly, D., Du, Z., Sims, M., Yang, C.H., Interiano, R.B., Davidoff, A.M., and Pfeffer, L.M. (2015). Molecular heterogeneity in a patient-derived glioblastoma xenoline is regulated by different cancer stem cell populations. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145052"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3390\/cancers6010376","article-title":"STAT3 Activation in Glioblastoma: Biochemical and Therapeutic Implications","volume":"6","author":"Kim","year":"2014","journal-title":"Cancers"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1126\/science.1164551","article-title":"Function of mitochondrial Stat3 in cellular respiration","volume":"323","author":"Wegrzyn","year":"2009","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6029","DOI":"10.1038\/onc.2015.98","article-title":"Emerging strategies for cancer immunoprevention","volume":"34","author":"Roeser","year":"2015","journal-title":"Oncogene"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26167","DOI":"10.1074\/jbc.M113.477950","article-title":"Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappaB signaling in glioblastoma cancer stem cells regulates the Notch pathway","volume":"288","author":"Garner","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1002\/stem.2909","article-title":"Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells","volume":"36","author":"Ganguly","year":"2018","journal-title":"Stem Cells"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrd4088","article-title":"Therapeutic modulators of STAT signalling for human diseases","volume":"12","author":"Miklossy","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215614","DOI":"10.1016\/j.canlet.2022.215614","article-title":"SS-4 is a highly selective small molecule inhibitor of STAT3 tyrosine phosphorylation that potently inhibits GBM tumorigenesis in vitro and in vivo","volume":"533","author":"Wang","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1016\/j.cell.2021.03.023","article-title":"Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion","volume":"184","author":"Gangoso","year":"2021","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"djw144","DOI":"10.1093\/jnci\/djw144","article-title":"Genomic Analysis of Immune Cell Infiltrates Across 11 Tumor Types","volume":"108","author":"Iglesia","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1593\/neo.13706","article-title":"The IL-6\/JAK\/Stat3 feed-forward loop drives tumorigenesis and metastasis","volume":"15","author":"Chang","year":"2013","journal-title":"Neoplasia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40425-018-0316-z","article-title":"Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: A comprehensive review of registration trials and future considerations","volume":"6","author":"Gong","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eaav7816","DOI":"10.1126\/scitranslmed.aav7816","article-title":"Sensitization to immune checkpoint blockade through activation of a STAT1\/NK axis in the tumor microenvironment","volume":"11","author":"Zemek","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.trecan.2018.11.002","article-title":"Glioblastoma Therapy in the Age of Molecular Medicine","volume":"5","author":"Geraldo","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/s41580-019-0123-5","article-title":"Metabolic regulation of cell growth and proliferation","volume":"20","author":"Zhu","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cell.2018.09.048","article-title":"Biological Functions of Autophagy Genes: A Disease Perspective","volume":"176","author":"Levine","year":"2019","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lei, Y., and Klionsky, D.J. (2021). The Emerging Roles of Autophagy in Human Diseases. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111651"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"166262","DOI":"10.1016\/j.bbadis.2021.166262","article-title":"A perspective on the role of autophagy in cancer","volume":"1867","author":"Ariosa","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Yu, G., and Klionsky, D.J. (2022). Life and Death Decisions-The Many Faces of Autophagy in Cell Survival and Cell Death. Biomolecules, 12.","DOI":"10.3390\/biom12070866"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41556-018-0037-z","article-title":"Cargo recognition and degradation by selective autophagy","volume":"20","author":"Gatica","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.jmb.2016.02.021","article-title":"An overview of macroautophagy in yeast","volume":"428","author":"Wen","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lei, Y., Huang, Y., Wen, X., Yin, Z., Zhang, Z., and Klionsky, D.J. (2022). How Cells Deal with the Fluctuating Environment: Autophagy Regulation under Stress in Yeast and Mammalian Systems. Antioxidants, 11.","DOI":"10.3390\/antiox11020304"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jmb.2019.06.001","article-title":"Ribosome Abundance Control Via the Ubiquitin-Proteasome System and Autophagy","volume":"432","author":"An","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yin, Z., Popelka, H., Lei, Y., Yang, Y., and Klionsky, D.J. (2020). The Roles of Ubiquitin in Mediating Autophagy. Cells, 9.","DOI":"10.3390\/cells9092025"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/s41580-018-0001-6","article-title":"The coming of age of chaperone-mediated autophagy","volume":"19","author":"Kaushik","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41580-022-00529-z","article-title":"The emerging mechanisms and functions of microautophagy","volume":"24","author":"Wang","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1111\/j.1600-0854.2005.00337.x","article-title":"Unifying nomenclature for the isoforms of the lysosomal membrane protein LAMP-2","volume":"6","author":"Eskelinen","year":"2005","journal-title":"Traffic"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1038\/s41598-017-01246-w","article-title":"Basal autophagy prevents autoactivation or enhancement of inflammatory signals by targeting monomeric MyD88","volume":"7","author":"Into","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.devcel.2015.11.010","article-title":"Role for Lipid Droplet Biogenesis and Microlipophagy in Adaptation to Lipid Imbalance in Yeast","volume":"35","author":"Vevea","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41580-021-00392-4","article-title":"Machinery, regulation and pathophysiological implications of autophagosome maturation","volume":"22","author":"Zhao","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.tibs.2013.12.001","article-title":"At the end of the autophagic road: An emerging understanding of lysosomal functions in autophagy","volume":"39","author":"Shen","year":"2014","journal-title":"Trends Biochem. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.bbamcr.2009.01.006","article-title":"Anti- and pro-tumor functions of autophagy","volume":"1793","author":"Morselli","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"856","DOI":"10.15252\/embj.201490784","article-title":"Autophagy in malignant transformation and cancer progression","volume":"34","author":"Galluzzi","year":"2015","journal-title":"EMBO J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1111\/febs.14388","article-title":"Functions of autophagy in the tumor microenvironment and cancer metastasis","volume":"285","author":"Mowers","year":"2018","journal-title":"FEBS J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jbior.2012.10.001","article-title":"Deconstructing mTOR complexes in regulation of Glioblastoma Multiforme and its stem cells","volume":"53","author":"Jeevan","year":"2013","journal-title":"Adv. Biol. Regul."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"22455","DOI":"10.1038\/srep22455","article-title":"Suppression of the invasive potential of Glioblastoma cells by mTOR inhibitors involves modulation of NFkappaB and PKC-alpha signaling","volume":"6","author":"Chandrika","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neuroscience.2017.01.032","article-title":"The PI3K inhibitor GDC-0941 enhances radiosensitization and reduces chemoresistance to temozolomide in GBM cell lines","volume":"346","author":"Shi","year":"2017","journal-title":"Neuroscience"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1080\/15548627.2016.1190053","article-title":"Suppression of autophagy impedes glioblastoma development and induces senescence","volume":"12","author":"Gammoh","year":"2016","journal-title":"Autophagy"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/j.molonc.2015.04.016","article-title":"Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells","volume":"9","author":"Catalano","year":"2015","journal-title":"Mol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"467","DOI":"10.4161\/auto.5668","article-title":"Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3","volume":"4","author":"Aoki","year":"2008","journal-title":"Autophagy"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"208076","DOI":"10.1155\/2015\/208076","article-title":"Combined epidermal growth factor receptor and Beclin1 autophagic protein expression analysis identifies different clinical presentations, responses to chemo- and radiotherapy, and prognosis in glioblastoma","volume":"2015","author":"Tini","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/bjc.2017.263","article-title":"Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A","volume":"117","author":"Dirkse","year":"2017","journal-title":"Br. J. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4161\/auto.5278","article-title":"Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3","volume":"4","author":"Azad","year":"2008","journal-title":"Autophagy"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"411","DOI":"10.3892\/mmr.2014.2151","article-title":"Temozolomide induces autophagy via ATM-AMPK-ULK1 pathways in glioma","volume":"10","author":"Zou","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.bcp.2019.03.015","article-title":"Late autophagy inhibitor chloroquine improves efficacy of the histone deacetylase inhibitor SAHA and temozolomide in gliomas","volume":"163","author":"Goncalves","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1101\/gad.287524.116","article-title":"Recent insights into the function of autophagy in cancer","volume":"30","author":"Amaravadi","year":"2016","journal-title":"Genes Dev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5610","DOI":"10.1158\/0008-5472.CAN-16-0722","article-title":"The Challenge of Developing Autophagy Inhibition as a Therapeutic Strategy","volume":"76","author":"Gewirtz","year":"2016","journal-title":"Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nature09781","article-title":"Cells of origin in cancer","volume":"469","author":"Visvader","year":"2011","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wang, X., Lee, J., and Xie, C. (2022). Autophagy Regulation on Cancer Stem Cell Maintenance, Metastasis, and Therapy Resistance. Cancers, 14.","DOI":"10.3390\/cancers14020381"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cmet.2022.01.007","article-title":"The hallmarks of cancer metabolism: Still emerging","volume":"34","author":"Pavlova","year":"2022","journal-title":"Cell Metab."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Vieira de Castro, J., Goncalves, C.S., Hormigo, A., and Costa, B.M. (2020). Exploiting the Complexities of Glioblastoma Stem Cells: Insights for Cancer Initiation and Therapeutic Targeting. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155278"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"LiCausi, F., and Hartman, N.W. (2018). Role of mTOR Complexes in Neurogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051544"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Barzegar Behrooz, A., Talaie, Z., Jusheghani, F., Los, M.J., Klonisch, T., and Ghavami, S. (2022). Wnt and PI3K\/Akt\/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031353"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1200\/JCO.2004.07.193","article-title":"The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas","volume":"22","author":"Chakravarti","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/embor.2011.39","article-title":"Secreted factors from brain endothelial cells maintain glioblastoma stem-like cell expansion through the mTOR pathway","volume":"12","author":"Thirant","year":"2011","journal-title":"EMBO Rep."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Ryskalin, L., Gaglione, A., Limanaqi, F., Biagioni, F., Familiari, P., Frati, A., Esposito, V., and Fornai, F. (2019). The Autophagy Status of Cancer Stem Cells in Gliobastoma Multiforme: From Cancer Promotion to Therapeutic Strategies. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153824"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.celrep.2013.09.017","article-title":"mTORC1 targets the translational repressor 4E-BP2, but not S6 kinase 1\/2, to regulate neural stem cell self-renewal in vivo","volume":"5","author":"Hartman","year":"2013","journal-title":"Cell Rep."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.devcel.2020.06.010","article-title":"The Lysosome at the Intersection of Cellular Growth and Destruction","volume":"54","author":"Shin","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.molcel.2014.06.002","article-title":"Cytosolic pH regulates cell growth through distinct GTPases, Arf1 and Gtr1, to promote Ras\/PKA and TORC1 activity","volume":"55","author":"Dechant","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1038\/emboj.2010.138","article-title":"Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V-ATPase","volume":"29","author":"Dechant","year":"2010","journal-title":"EMBO J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"18106","DOI":"10.18632\/aging.203362","article-title":"Autophagy inhibition reinforces stemness together with exit from dormancy of polydisperse glioblastoma stem cells","volume":"13","author":"Brunel","year":"2021","journal-title":"Aging"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/PPO.0000000000000020","article-title":"Molecular genetics of gliomas","volume":"20","author":"Appin","year":"2014","journal-title":"Cancer J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1093\/neuonc\/noab001","article-title":"PTEN deficiency leads to proteasome addiction: A novel vulnerability in glioblastoma","volume":"23","author":"Benitez","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1111\/jcmm.17421","article-title":"STAT3 suppresses the AMPKalpha\/ULK1-dependent induction of autophagy in glioblastoma cells","volume":"26","author":"Bhattacharya","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1016\/j.devcel.2022.05.007","article-title":"PDGF signaling inhibits mitophagy in glioblastoma stem cells through N(6)-methyladenosine","volume":"57","author":"Lv","year":"2022","journal-title":"Dev. Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5218","DOI":"10.1158\/0008-5472.CAN-19-0198","article-title":"Mitochondrial NIX Promotes Tumor Survival in the Hypoxic Niche of Glioblastoma","volume":"79","author":"Jung","year":"2019","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e54006","DOI":"10.15252\/embr.202154006","article-title":"Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells","volume":"24","author":"Liu","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1158\/0008-5472.CAN-21-2161","article-title":"Chaperone-Mediated Autophagy Controls Proteomic and Transcriptomic Pathways to Maintain Glioma Stem Cell Activity","volume":"82","author":"Azkargorta","year":"2022","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1186\/s12967-015-0627-5","article-title":"Effect of the JAK2\/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres","volume":"13","author":"Mukthavaram","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"496","DOI":"10.4161\/auto.4602","article-title":"Roles of mTOR and STAT3 in autophagy induced by telomere 3\u2032 overhang-specific DNA oligonucleotides","volume":"3","author":"Yokoyama","year":"2007","journal-title":"Autophagy"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.yexcr.2014.09.006","article-title":"Suppression of autophagy augments the radiosensitizing effects of STAT3 inhibition on human glioma cells","volume":"330","author":"Yuan","year":"2015","journal-title":"Exp. 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