{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T22:17:12Z","timestamp":1775341032699,"version":"3.50.1"},"reference-count":88,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FEDER RTI2018-099873-B-I00"],"award-info":[{"award-number":["FEDER RTI2018-099873-B-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["FEDER SA125P20"],"award-info":[{"award-number":["FEDER SA125P20"]}],"id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Autophagy is a physiological process by which various damaged or non-essential cytosolic components are recycled, contributing to cell survival under stress conditions. In cancer, autophagy can have antitumor or protumor effects depending on the developmental stage. Here, we use Western blotting, immunochemistry, and transmission electron microscopy to demonstrate that the antitumor peptide TAT-Cx43266-283, a c-Src inhibitor, blocks autophagic flux in glioblastoma stem cells (GSCs) under basal and nutrient-deprived conditions. Upon nutrient deprivation, GSCs acquired a dormant-like phenotype that was disrupted by inhibition of autophagy with TAT-Cx43266-283 or chloroquine (a classic autophagy inhibitor), leading to GSC death. Remarkably, dasatinib, a clinically available c-Src inhibitor, could not replicate TAT-Cx43266-283 effect on dormant GSCs, revealing for the first time the possible involvement of pathways other than c-Src in TAT-Cx43266-283 effect. TAT-Cx43266-283 exerts an antitumor effect both in nutrient-complete and nutrient-deprived environments, which constitutes an advantage over chloroquine and dasatinib, whose effects depend on nutrient environment. Finally, our analysis of the levels of autophagy-related proteins in healthy and glioma donors suggests that autophagy is upregulated in glioblastoma, further supporting the interest in inhibiting this process in the most aggressive brain tumor and the potential use of TAT-Cx43266-283 as a therapy for this type of cancer.<\/jats:p>","DOI":"10.3390\/cancers13174262","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"4262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Impairment of Autophagic Flux Participates in the Antitumor Effects of TAT-Cx43266-283 in Glioblastoma Stem Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6908-3172","authenticated-orcid":false,"given":"Sara G.","family":"Pelaz","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, Calle Pintor Fernando Gallego 1, 37007 Salamanca, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Hospital Virgen de la Vega, 10\u00aa Planta, Paseo de San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7319-4913","authenticated-orcid":false,"given":"Claudia","family":"Ollauri-Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, Calle Pintor Fernando Gallego 1, 37007 Salamanca, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Hospital Virgen de la Vega, 10\u00aa Planta, Paseo de San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-9826","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Lillo","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, Calle Pintor Fernando Gallego 1, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Hospital Virgen de la Vega, 10\u00aa Planta, Paseo de San Vicente 58-182, 37007 Salamanca, Spain"},{"name":"Departamento de Biolog\u00eda Celular y Patolog\u00eda, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6302-6134","authenticated-orcid":false,"given":"Arantxa","family":"Tabernero","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias de Castilla y Le\u00f3n (INCYL), Universidad de Salamanca, Calle Pintor Fernando Gallego 1, 37007 Salamanca, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), Hospital Virgen de la Vega, 10\u00aa Planta, Paseo de San Vicente 58-182, 37007 Salamanca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1308573","article-title":"A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma","volume":"370","author":"Gilbert","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nature11287","article-title":"A restricted cell population propagates glioblastoma growth after chemotherapy","volume":"488","author":"Chen","year":"2012","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/nature05236","article-title":"Glioma stem cells promote radioresistance by preferential activation of the DNA damage response","volume":"444","author":"Bao","year":"2006","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1101\/gad.261982.115","article-title":"Cancer stem cells in glioblastoma","volume":"29","author":"Lathia","year":"2015","journal-title":"Genes Dev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.neuroscience.2015.02.029","article-title":"The role of connexin43\u2013Src interaction in astrocytomas: A molecular puzzle","volume":"323","author":"Tabernero","year":"2016","journal-title":"Neuroscience"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1242\/jcs.01111","article-title":"Newest findings on the oldest oncogene; how activated src does it","volume":"117","author":"Frame","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1038\/sj.onc.1201168","article-title":"Development and malignant progression of astrocytomas in GFAP-v-src transgenic mice","volume":"14","author":"Weissenberger","year":"1997","journal-title":"Oncogene"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49819","DOI":"10.18632\/oncotarget.10454","article-title":"Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes","volume":"7","author":"Prieto","year":"2016","journal-title":"Oncotarget"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1023","DOI":"10.1038\/cddis.2013.560","article-title":"A cell-penetrating peptide based on the interaction between c-Src and connexin43 reverses glioma stem cell phenotype","volume":"5","author":"Gangoso","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.1038\/onc.2010.299","article-title":"Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells","volume":"29","author":"Gangoso","year":"2010","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/1098-1136(200102)33:2<107::AID-GLIA1010>3.0.CO;2-4","article-title":"Reduced expression of connexin-43 and functional gap junction coupling in human gliomas","volume":"33","author":"Soroceanu","year":"2001","journal-title":"Glia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3892\/ijo.2014.2432","article-title":"The role of Src family kinases in growth and migration of glioma stem cells","volume":"45","author":"Han","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.stemcr.2017.06.007","article-title":"A Short Region of Connexin43 Reduces Human Glioma Stem Cell Migration, Invasion, and Survival through Src, PTEN, and FAK","volume":"9","author":"Tabernero","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nbt.1513","article-title":"Bead-based profiling of tyrosine kinase phosphorylation identifies SRC as a potential target for glioblastoma therapy","volume":"27","author":"Du","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1073\/pnas.88.5.1883","article-title":"Transfection of C6 glioma-cells with connexin-43 cDNA\u2013analysis of expression, intercellular coupling, and cell-proliferation","volume":"88","author":"Zhu","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/stem.1685","article-title":"Connexin 43 Reverses Malignant Phenotypes of Glioma Stem Cells by Modulating E-Cadherin","volume":"30","author":"Yu","year":"2011","journal-title":"Stem Cells"},{"key":"ref_18","first-page":"4208","article-title":"Invivo Growth of C6 Glioma-Cells Transfected with Connexin43 cDNA","volume":"52","author":"Naus","year":"1992","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"16010","DOI":"10.1074\/jbc.272.25.16010","article-title":"A Truncated HIV-1 Tat Protein Basic Domain Rapidly Translocates through the Plasma Membrane and Accumulates in the Cell Nucleus","volume":"272","author":"Brodin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"22824","DOI":"10.1074\/jbc.272.36.22824","article-title":"Tyrosine Phosphorylation of Connexin 43 by v-Src Is Mediated by SH2 and SH3 Domain Interactions","volume":"272","author":"Kanemitsu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103134","DOI":"10.1016\/j.ebiom.2020.103134","article-title":"Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43266-283","volume":"62","author":"Pelaz","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_22","first-page":"493","article-title":"Connexin43 peptide, TAT-Cx43266\u2013283, selectively targets glioma cells, impairs malignant growth, and enhances survival in mouse models in vivo","volume":"22","author":"Pelaz","year":"2019","journal-title":"Neuro-Oncology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1089\/ars.2013.5371","article-title":"An Overview of Autophagy: Morphology, Mechanism, and Regulation","volume":"20","author":"Parzych","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 Binds Directly to Atg8\/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1158\/1078-0432.CCR-13-2438","article-title":"Molecular Pathways: Autophagy in Cancer\u2014A Matter of Timing and Context","volume":"21","author":"Cicchini","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1158\/1535-7163.MCT-11-0047","article-title":"The Role of Autophagy in Cancer: Therapeutic Implications","volume":"10","author":"Yang","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41418-019-0474-7","article-title":"Autophagy in cancer: Moving from understanding mechanism to improving therapy responses in patients","volume":"27","author":"Levy","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"60987","DOI":"10.18632\/oncotarget.17719","article-title":"Autophagy-related gene expression is an independent prognostic indicator of glioma","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/OTT.S238332","article-title":"Prognostic Correlation of Autophagy-Related Gene Expression-Based Risk Signature in Patients with Glioblastoma","volume":"13","author":"Wang","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1111\/jcmm.14938","article-title":"A risk signature with four autophagy-related genes for predicting survival of glioblastoma multiforme","volume":"24","author":"Wang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s12253-017-0310-7","article-title":"High LC3\/Beclin Expression Correlates with Poor Survival in Glioma: A Definitive Role for Autophagy as Evidenced by In Vitro Autophagic Flux","volume":"25","author":"Cj","year":"2017","journal-title":"Pathol. Oncol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-0864-7","article-title":"Inhibition of autophagy increases susceptibility of glioblastoma stem cells to temozolomide by igniting ferroptosis","volume":"9","author":"Buccarelli","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_33","first-page":"862","article-title":"Immunohistochemical assessment of autophagic protein LC3B and p62 levels in glioma patients","volume":"11","author":"Jiang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.21873\/anticanres.13233","article-title":"Clinicopathological Significance of Autophagy-related Proteins and its Association With Genetic Alterations in Gliomas","volume":"39","author":"Tamrakar","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3389\/fonc.2021.627023","article-title":"Autophagy and Cancer Dormancy","volume":"11","author":"Akkoc","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_36","first-page":"1","article-title":"Autophagy promotes the survival of dormant breast cancer cells and metastatic tumour recurrence","volume":"9","author":"Ramirez","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.stem.2019.06.004","article-title":"GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile","volume":"25","author":"Rusu","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_38","first-page":"1","article-title":"Autophagy mediates glucose starvation-induced glioblastoma cell quiescence and chemoresistance through coordinating cell metabolism, cell cycle, and survival","volume":"9","author":"Wang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.surneu.2006.08.080","article-title":"Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme","volume":"67","author":"Calderon","year":"2007","journal-title":"Surg. Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"337","DOI":"10.7326\/0003-4819-144-5-200603070-00008","article-title":"Adding Chloroquine to Conventional Treatment for Glioblastoma Multiforme","volume":"144","author":"Sotelo","year":"2006","journal-title":"Ann. Intern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.4161\/auto.28984","article-title":"A phase I\/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme","volume":"10","author":"Rosenfeld","year":"2014","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Compter, I., Eekers, D.B.P., Hoeben, A., Rouschop, K.M.A., Reymen, B., Ackermans, L., Beckervordersantforth, J., Bauer, N.J.C., Anten, M.M., and Wesseling, P. (2020). Chloroquine combined with concurrent radiotherapy and temozolomide for newly diagnosed glioblastoma: A phase IB trial. Autophagy, 1\u20139.","DOI":"10.1080\/15548627.2020.1816343"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.molmed.2007.08.002","article-title":"TAT transduction: The molecular mechanism and therapeutic prospects","volume":"13","author":"Gump","year":"2007","journal-title":"Trends Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Tissue-based map of the human proteome","volume":"347","author":"Fagerberg","year":"2015","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eaal3321","DOI":"10.1126\/science.aal3321","article-title":"A subcellular map of the human proteome","volume":"356","author":"Thul","year":"2017","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"eaan2507","DOI":"10.1126\/science.aan2507","article-title":"A pathology atlas of the human cancer transcriptome","volume":"357","author":"Uhlen","year":"2017","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/pro.3307","article-title":"The human protein atlas: A spatial map of the human proteome","volume":"27","author":"Thul","year":"2017","journal-title":"Protein Sci."},{"key":"ref_49","unstructured":"R Core Team (2021, May 11). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna. Available online: https:\/\/www.scirp.org\/(S(i43dyn45teexjx455qlt3d2q))\/reference\/ReferencesPapers.aspx?ReferenceID=1787696."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.12688\/f1000research.15789.1","article-title":"TRGAted: A web tool for survival analysis using protein data in the Cancer Genome Atlas","volume":"7","author":"Borcherding","year":"2018","journal-title":"F1000Research"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nmeth.2650","article-title":"TCPA: A resource for cancer functional proteomics data","volume":"10","author":"Li","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_52","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_53","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.canlet.2010.08.014","article-title":"Targeting SRC in glioblastoma tumors and brain metastases: Rationale and preclinical studies","volume":"298","author":"Ahluwalia","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1158\/0008-5472.CAN-07-1182","article-title":"The Protein Phosphatase Activity of PTEN Regulates Src Family Kinases and Controls Glioma Migration","volume":"68","author":"Dey","year":"2008","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11060-005-9068-y","article-title":"Reduced Glioma Infiltration in Src-deficient Mice","volume":"78","author":"Lund","year":"2006","journal-title":"J. Neuro-Oncology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/path.2694","article-title":"Autophagy: Assays and artifacts","volume":"221","author":"Barth","year":"2010","journal-title":"J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4161\/auto.4600","article-title":"How to Interpret LC3 Immunoblotting","volume":"3","author":"Mizushima","year":"2007","journal-title":"Autophagy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.ctrv.2010.02.015","article-title":"Dasatinib: A potent SRC inhibitor in clinical development for the treatment of solid tumors","volume":"36","author":"Araujo","year":"2010","journal-title":"Cancer Treat. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1242\/jcs.168153","article-title":"Ambra1 at a glance","volume":"128","author":"Cianfanelli","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4161\/auto.27419","article-title":"Detection ofWIPI1mRNA as an indicator of autophagosome formation","volume":"10","author":"Tsuyuki","year":"2013","journal-title":"Autophagy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13599","DOI":"10.1074\/jbc.M117.782276","article-title":"Accumulation of autophagosomes confers cytotoxicity","volume":"292","author":"Button","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"ra81","DOI":"10.1126\/scisignal.2001017","article-title":"Akt and Autophagy Cooperate to Promote Survival of Drug-Resistant Glioma","volume":"3","author":"Fan","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"109774","DOI":"10.1016\/j.cellsig.2020.109774","article-title":"The promoting role of lysosome-localized c-Src in autophagosome-lysosome fusion","volume":"75","author":"Suzuki","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/sj.bjc.6604676","article-title":"Effects of dasatinib on EphA2 receptor tyrosine kinase activity and downstream signalling in pancreatic cancer","volume":"99","author":"Chang","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_66","first-page":"156","article-title":"Combined SFK\/MEK inhibition prevents metastatic outgrowth of dormant tumor cells","volume":"124","author":"Vieira","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1158\/1078-0432.CCR-10-2574","article-title":"ERK1\/2 and p38\u03b1\/\u03b2 Signaling in Tumor Cell Quiescence: Opportunities to Control Dormant Residual Disease","volume":"17","author":"Sosa","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_68","first-page":"1684","article-title":"ERKMAPK Activity as a Determinant of Tumor Growth and Dormancy; Regulation by p38SAPK","volume":"63","author":"Estrada","year":"2003","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1091\/mbc.12.4.863","article-title":"Urokinase Receptor and Fibronectin Regulate the ERKMAPK to p38MAPK Activity Ratios That Determine Carcinoma Cell Proliferation or Dormancy In Vivo","volume":"12","author":"Liu","year":"2001","journal-title":"Mol. Biol. Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1038\/ncomms3799","article-title":"Autophagy proteins regulate ERK phosphorylation","volume":"4","author":"Athonvarangkul","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB Links Autophagy to Lysosomal Biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.4161\/auto.21857","article-title":"MAPK15\/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins","volume":"8","author":"Colecchia","year":"2012","journal-title":"Autophagy"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.cmet.2006.01.011","article-title":"Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62","volume":"3","author":"Rodriguez","year":"2006","journal-title":"Cell Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms5425","article-title":"Src-dependent impairment of autophagy by oxidative stress in a mouse model of Duchenne muscular dystrophy","volume":"5","author":"Pal","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s00253-019-10257-8","article-title":"Targeting PI3K\/AKT\/mTOR-mediated autophagy for tumor therapy","volume":"104","author":"Xu","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5157","DOI":"10.18632\/oncotarget.6986","article-title":"Dual PI-3 kinase\/mTOR inhibition impairs autophagy flux and induces cell death independent of apoptosis and necroptosis","volume":"7","author":"Button","year":"2016","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-06844-4","article-title":"Src regulates amino acid-mediated mTORC1 activation by disrupting GATOR1-Rag GTPase interaction","volume":"9","author":"Pal","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1074\/jbc.271.7.3779","article-title":"Characterization of the Mitogen-activated Protein Kinase Phosphorylation Sites on the Connexin-43 Gap Junction Protein","volume":"271","author":"Lampe","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.4161\/auto.5.8.9896","article-title":"Autophagy, senescence and tumor dormancy in cancer therapy","volume":"5","author":"Gewirtz","year":"2009","journal-title":"Autophagy"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5835","DOI":"10.1096\/fj.201701568R","article-title":"Reverting the molecular fingerprint of tumor dormancy as a therapeutic strategy for glioblastoma","volume":"32","author":"Tiram","year":"2018","journal-title":"FASEB J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"jcs222836","DOI":"10.1242\/jcs.222836","article-title":"p62\/SQSTM1\u2013steering the cell through health and disease","volume":"131","author":"Komatsu","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1101\/gad.237354.113","article-title":"p62\/SQSTM1 synergizes with autophagy for tumor growth in vivo","volume":"28","author":"Wei","year":"2014","journal-title":"Genes Dev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ccr.2008.02.001","article-title":"The Signaling Adaptor p62 Is an Important NF-\u03baB Mediator in Tumorigenesis","volume":"13","author":"Duran","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1126\/science.1193497","article-title":"Autophagy and Metabolism","volume":"330","author":"Rabinowitz","year":"2010","journal-title":"Science"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.cmet.2019.03.003","article-title":"Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism","volume":"29","author":"Lahiri","year":"2019","journal-title":"Cell Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.cell.2014.11.006","article-title":"Metabolic Control of Autophagy","volume":"159","author":"Galluzzi","year":"2014","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1093\/neuonc\/nov011","article-title":"Phase 2 trial of dasatinib in target-selected patients with recurrent glioblastoma (RTOG 0627)","volume":"17","author":"Lassman","year":"2015","journal-title":"Neuro-Oncology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1126\/science.aar5986","article-title":"The nutrient environment affects therapy","volume":"360","author":"Muir","year":"2018","journal-title":"Science"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4262\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:50:46Z","timestamp":1760165446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/17\/4262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":88,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["cancers13174262"],"URL":"https:\/\/doi.org\/10.3390\/cancers13174262","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]}}}