{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:53Z","timestamp":1788844253651,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor clinical outcomes and limited responsiveness to conventional treatments. Beyond delayed diagnosis, its high mortality is linked to limited treatment choices and resistance to chemotherapy. Neoplastic cells characterized by stem-like features and epithelial\u2013mesenchymal transition (EMT) activation are crucial drivers of drug resistance and metastatic progression. Consequently, targeting these cellular programs could represent a promising therapeutic strategy for PDAC. N-acetyl-L-aspartic acid (NAA) is an endogenous metabolite, mainly localized in the central nervous system, where it facilitates acetate storage for lipid metabolism. Previous studies established its antineoplastic effect in neuroblastoma, promoting a more differentiated phenotype of cancer cells. Here we investigated the effects of NAA on BxPC-3 pancreatic cancer cells using both 2D and 3D models. NAA treatment induced a dose-dependent reduction in cell proliferation and led to a significant downregulation of stemness-associated surface markers, with concomitant upregulation of E-cadherin. Furthermore, NAA significantly enhanced cellular radiosensitization with a reduction in caveolin-1 and increased efficacy of gemcitabine in PDAC cells. Collectively, these results confirmed the anticancer activity of NAA and provide a rationale for further investigation of its synergistic effects with radiotherapy to yield better PDAC treatments.<\/jats:p>","DOI":"10.3390\/cells15171616","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["N-Acetyl Aspartic Acid (NAA) Attenuates Stemness and Epithelial\u2013Mesenchymal Transition and Enhances Radio- and Chemo-Sensitivity in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Fabiana","family":"Crispo","sequence":"first","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2199-6838","authenticated-orcid":false,"given":"Rosa","family":"Lioy","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7061-0749","authenticated-orcid":false,"given":"Rosalia","family":"Dieli","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4831-3252","authenticated-orcid":false,"given":"Mara","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Carlo","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0643-5684","authenticated-orcid":false,"given":"Antonella","family":"Bianculli","sequence":"additional","affiliation":[{"name":"Physic Unit, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7961-6973","authenticated-orcid":false,"given":"Vincenzo","family":"De Fina","sequence":"additional","affiliation":[{"name":"Physic Unit, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-2007","authenticated-orcid":false,"given":"Grazia","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7389-4109","authenticated-orcid":false,"given":"Vito","family":"Metallo","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Donatella","family":"Telesca","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0299-6145","authenticated-orcid":false,"given":"Gennaro","family":"Laus","sequence":"additional","affiliation":[{"name":"Department of Services, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Simona","family":"Loperte","sequence":"additional","affiliation":[{"name":"Institute of Methodologies for Environmental Research, National Research Council of Italy, 85050 Tito Scalo, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Rosa","family":"Lerose","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Carmela","family":"Mazzoccoli","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, IRCCS-CROB, Centro Di Riferimento Oncologico della Basilicata, 85028 Rionero in Vulture, PZ, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1001\/jama.2021.13027","article-title":"Pancreatic Cancer: A Review","volume":"326","author":"Park","year":"2021","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s12029-025-01183-2","article-title":"Trends in the Global Incidence of Pancreatic Cancer and a Brief Review of Its Histologic and Molecular Subtypes","volume":"56","author":"Leiphrakpam","year":"2025","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_3","first-page":"12","article-title":"Cancer Statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yu, W., Zhou, D., Meng, F., Wang, J., Wang, B., Qiang, J., Shen, L., Wang, M., and Fang, H. (2025). The Global, Regional Burden of Pancreatic Cancer and Its Attributable Risk Factors from 1990 to 2021. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-13471-y"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/SLA.0000000000003284","article-title":"Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline\/Locally Advanced Pancreatic Cancer","volume":"273","author":"Truty","year":"2021","journal-title":"Ann. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.annonc.2023.08.009","article-title":"Pancreatic Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up","volume":"34","author":"Conroy","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102973","DOI":"10.1016\/j.ctrv.2025.102973","article-title":"Medical Management of Pancreatic Cancer: From Personalization to Broadening Treatment Strategies","volume":"138","author":"Dusetti","year":"2025","journal-title":"Cancer Treat. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Moffett, J.R., Arun, P., Ariyannur, P.S., and Namboodiri, A.M.A. (2013). N-Acetylaspartate Reductions in Brain Injury: Impact on Post-Injury Neuroenergetics, Lipid Synthesis, and Protein Acetylation. Front. Neuroenerg., 5.","DOI":"10.3389\/fnene.2013.00011"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13808","DOI":"10.1096\/fj.201801323R","article-title":"N-Acetylaspartate Availability Is Essential for Juvenile Survival on Fat-Free Diet and Determines Metabolic Health","volume":"33","author":"Hofer","year":"2019","journal-title":"FASEB J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Appu, A.P., Moffett, J.R., Arun, P., Moran, S., Nambiar, V., Krishnan, J.K.S., Puthillathu, N., and Namboodiri, A.M.A. (2017). Increasing N-Acetylaspartate in the Brain during Postnatal Myelination Does Not Cause the Cns Pathologies of Canavan Disease. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00161"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pneurobio.2006.12.003","article-title":"N-Acetylaspartate in the CNS: From Neurodiagnostics to Neurobiology","volume":"81","author":"Moffett","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s11033-007-9167-2","article-title":"Upregulation of N-Acetylaspartic Acid Alters Inflammation, Transcription and Contractile Associated Protein Levels in the Stomach and Smooth Muscle Contractility","volume":"36","author":"Surendran","year":"2009","journal-title":"Mol. Biol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"36040","DOI":"10.1074\/jbc.M113.491324","article-title":"NAT8L (N-Acetyltransferase 8-like) Accelerates Lipid Turnover and Increases Energy Expenditure in Brown Adipocytes","volume":"288","author":"Pessentheiner","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23723","DOI":"10.1038\/srep23723","article-title":"N-Acetylaspartate Catabolism Determines Cytosolic Acetyl-CoA Levels and Histone Acetylation in Brown Adipocytes","volume":"6","author":"Prokesch","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bogner-Strauss, J.G. (2017). N-Acetylaspartate Metabolism Outside the Brain: Lipogenesis, Histone Acetylation, and Cancer. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00240"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chang, C.K., Shih, T.T.F., Tien, Y.W., Chang, M.C., Chang, Y.T., Yang, S.H., Cheng, M.F., and Chen, B.-B. (2021). Metabolic Alterations in Pancreatic Cancer Detected by In Vivo 1H-Mr Spectroscopy: Correlation with Normal Pancreas, Pet Metabolic Activity, Clinical Stages, and Survival Outcome. Diagnostics, 11.","DOI":"10.3390\/diagnostics11091541"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1158\/2159-8290.CD-12-0345","article-title":"Cancer Cell Metabolism: One Hallmark, Many Faces","volume":"2","author":"Cantor","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103051","DOI":"10.1016\/j.copbio.2023.103051","article-title":"N-Acetyl-Aspartate Metabolism at the Interface of Cancer, Immunity, and Neurodegeneration","volume":"85","author":"Krause","year":"2024","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"djv426","DOI":"10.1093\/jnci\/djv426","article-title":"Role of Increased N-Acetylaspartate Levels in Cancer","volume":"108","author":"Zand","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40170-016-0150-z","article-title":"Bridging the Gap between Non-Targeted Stable Isotope Labeling and Metabolic Flux Analysis","volume":"4","author":"Weindl","year":"2016","journal-title":"Cancer Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1158\/1940-6207.CAPR-14-0287","article-title":"Cancer-Specific Production of n-Acetylaspartate via Nat8l Overexpression in Non-Small Cell Lung Cancer and Its Potential as a Circulating Biomarker","volume":"9","author":"Lou","year":"2016","journal-title":"Cancer Prev. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e51981","DOI":"10.15252\/embr.202051981","article-title":"N-acetylaspartate Release by Glutaminolytic Ovarian Cancer Cells Sustains Protumoral Macrophages","volume":"22","author":"Menga","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102585","DOI":"10.1016\/j.redox.2022.102585","article-title":"Hindering NAT8L Expression in Hepatocellular Carcinoma Increases Cytosolic Aspartate Delivery That Fosters Pentose Phosphate Pathway and Purine Biosynthesis Promoting Cell Proliferation","volume":"59","author":"Lazzarino","year":"2023","journal-title":"Redox Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26235","DOI":"10.18632\/oncotarget.8454","article-title":"N-Acetylaspartate (NAA) Induces Neuronal Differentiation of SH-SY5Y Neuroblastoma Cell Line and Sensitizes It to Chemotherapeutic Agents","volume":"7","author":"Mazzoccoli","year":"2016","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120024","DOI":"10.1016\/j.lfs.2021.120024","article-title":"N-Acetyl L-Aspartate and Triacetin Modulate Tumor Suppressor MicroRNA and Class I and II HDAC Gene Expression Induce Apoptosis in Glioblastoma Cancer Cells In Vitro","volume":"286","author":"Mekala","year":"2021","journal-title":"Life Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.3892\/etm.2017.4781","article-title":"ICELLigence Real-Time Cell Analysis System for Examining the Cytotoxicity of Drugs to Cancer Cell Lines","volume":"14","author":"Albeniz","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.toxrep.2020.02.002","article-title":"Real-Time Cell Analysis System in Cytotoxicity Applications: Usefulness and Comparison with Tetrazolium Salt Assays","volume":"7","author":"Ochocka","year":"2020","journal-title":"Toxicol. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1177\/1087057114557775","article-title":"Open Access to High-Content Clonogenic Analysis","volume":"20","author":"Ricci","year":"2015","journal-title":"J. Biomol. Screen."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2300354","DOI":"10.1002\/ardp.202300354","article-title":"Biological Evaluation of [4-(4-Aminophenyl)-1-(4-Fluorophenyl)-1H-Pyrrol-3-Yl](3,4,5-Trimethoxyphenyl)Methanone as Potential Antineoplastic Agent in 2D and 3D Breast Cancer Models","volume":"356","author":"Mazzoccoli","year":"2023","journal-title":"Arch. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1038\/cdd.2016.67","article-title":"TRAP1 Regulates Stemness through Wnt\/\u03b2-Catenin Pathway in Human Colorectal Carcinoma","volume":"23","author":"Lettini","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6577","DOI":"10.1158\/0008-5472.CAN-10-1256","article-title":"Mitochondrial Chaperone Trap1 and the Calcium Binding Protein Sorcin Interact and Protect Cells against Apoptosis Induced by Antiblastic Agents","volume":"70","author":"Landriscina","year":"2010","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Loh, C.Y., Chai, J.Y., Tang, T.F., Wong, W.F., Sethi, G., Shanmugam, M.K., Chong, P.P., and Looi, C.Y. (2019). The E-Cadherin and n-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges. Cells, 8.","DOI":"10.3390\/cells8101118"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1038\/modpathol.2011.74","article-title":"Loss of E-Cadherin Expression and Outcome among Patients with Resectable Pancreatic Adenocarcinomas","volume":"24","author":"Hong","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.stem.2007.06.002","article-title":"Distinct Populations of Cancer Stem Cells Determine Tumor Growth and Metastatic Activity in Human Pancreatic Cancer","volume":"1","author":"Hermann","year":"2007","journal-title":"Cell Stem Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2018.10.013","article-title":"CD133 as a Regulator of Cancer Metastasis through the Cancer Stem Cells","volume":"106","author":"Liou","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.radonc.2009.07.004","article-title":"Caveolin-1 Mediated Radioresistance of 3D Grown Pancreatic Cancer Cells","volume":"92","author":"Hehlgans","year":"2009","journal-title":"Radiother. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Zhu, H., Yue, J., Pan, Z., Wu, H., Cheng, Y., Lu, H., Ren, X., Yao, M., Shen, Z., and Yang, J.M. (2010). Involvement of Caveolin-1 in Repair of DNA Damage through Both Homologous Recombination and Non-Homologous End Joining. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012055"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"116492","DOI":"10.1016\/j.bcp.2024.116492","article-title":"Overcoming Therapy Resistance in Pancreatic Cancer: New Insights and Future Directions","volume":"229","author":"Patthey","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/14656566.2026.2657995","article-title":"Pancreatic Cancer: Emerging Small Molecule Pharmacotherapies","volume":"27","author":"Pokora","year":"2026","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1517\/14728222.2011.566216","article-title":"Overcoming Drug Resistance in Pancreatic Cancer","volume":"15","author":"Long","year":"2011","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","article-title":"Small Molecules in Targeted Cancer Therapy: Advances, Challenges, and Future Perspectives","volume":"6","author":"Zhong","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12943-017-0624-9","article-title":"The Epithelial to Mesenchymal Transition (EMT) and Cancer Stem Cells: Implication for Treatment Resistance in Pancreatic Cancer","volume":"16","author":"Zhou","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_43","first-page":"30241","article-title":"A Promising Breakthrough in Pancreatic Cancer Research: The Potential of Spheroids as 3D Models","volume":"15","author":"Jamshidi","year":"2025","journal-title":"BioImpacts"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10867","DOI":"10.1038\/srep10867","article-title":"Caveolin-1 Is Associated with Tumor Progression and Confers a Multi-Modality Resistance Phenotype in Pancreatic Cancer","volume":"5","author":"Chatterjee","year":"2015","journal-title":"Sci. Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/17\/1616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:29:47Z","timestamp":1788841787000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/17\/1616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,5]]},"references-count":44,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cells15171616"],"URL":"https:\/\/doi.org\/10.3390\/cells15171616","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,5]]}}}