{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T22:41:04Z","timestamp":1794609664595,"version":"4.9.1"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum K\u00f6ln","id":[{"id":"https:\/\/ror.org\/05mxhda18","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Therapeutic resistance in esophageal adenocarcinoma (EAC) remains poorly understood at the level of tumor-stroma interactions. We investigated whether cancer-associated fibroblast (CAF)-derived signaling contributes to chemoradiation resistance and adverse clinical outcomes in EAC, with a focus on the functional role of GDF15 within the CAF-secreted program.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Serum GDF15 levels were analyzed in EAC patients before and after neoadjuvant chemoradiotherapy according to the CROSS regimen, with prognostic relevance validated in an independent cohort and public datasets. Primary EAC CAFs, EAC cell lines, and patient-derived organoids (PDOs) were used to model tumor-stroma crosstalk in 2D and 3D co-culture systems. Compartment-specific transcriptomic and proteomic profiling identified CAF-regulated pathways. Genetic depletion and antibody-mediated neutralization of GDF15 were used to assess its functional contribution, followed by evaluation of chemoradiation sensitivity, mitochondrial function, oxidative phosphorylation dependency, and AKT pathway activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Serum GDF15 levels increased significantly following CROSS treatment, and elevated post-treatment GDF15 independently predicted poor overall survival in EAC patients. CAFs enhanced resistance to chemotherapy and radiotherapy in EAC cells and PDOs, accompanied by increased GDF15 secretion. Compartment-specific transcriptomic analysis and ELISA supported CAFs as a major source of inducible GDF15 during tumor-stroma interaction. Genetic depletion of GDF15 reduced treatment resistance, whereas recombinant GDF15 partially restored chemoresistance in GDF15-depleted models. GDF15 neutralization attenuated CAF-associated cisplatin tolerance. Mechanistically, GDF15 contributed to AKT activation and mitochondrial respiratory adaptation, including enhanced oxidative phosphorylation. Pharmacological attenuation of oxidative phosphorylation further sensitized EAC cells to cisplatin, particularly under CAF co-culture conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identifies CAF-derived GDF15 as a clinically relevant and functionally targetable component of a broader CAF-secreted resistance program in EAC. GDF15 contributes to AKT-associated mitochondrial adaptation and tumor cell tolerance to chemoradiation, while elevated post-CROSS serum GDF15 serves as a prognostic biomarker. These findings support further investigation of GDF15-directed and mitochondria-targeted strategies to overcome CAF-associated treatment resistance in esophageal adenocarcinoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-026-03776-6","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:08:40Z","timestamp":1784246920000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the CAF-GDF15 axis attenuates AKT-mediated mitochondrial rewiring and chemoradiation resistance in esophageal adenocarcinoma"],"prefix":"10.1186","volume":"45","author":[{"given":"Ningbo","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinwei","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhefang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Raatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar Velazquez","family":"Camacho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel M.","family":"Hillmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarete","family":"Odenthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong-Hien","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zicheng","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hun","family":"Chon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten F.","family":"Bijlsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Ros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanneke W. M.","family":"van Laarhoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Quaas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Wischhusen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-3402","authenticated-orcid":false,"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane J.","family":"Bruns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"3776_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2020","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2020;71:209\u201349. https:\/\/doi.org\/10.3322\/caac.21660.","journal-title":"CA Cancer J Clin"},{"key":"3776_CR2","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1038\/s41575-021-00419-3","volume":"18","author":"AP Thrift","year":"2021","unstructured":"Thrift AP. Global burden and epidemiology of Barrett oesophagus and oesophageal cancer. Nat Rev Gastroenterol Hepatol. 2021;18:432\u201343. https:\/\/doi.org\/10.1038\/s41575-021-00419-3.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"3776_CR3","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1007\/s12328-020-01237-x","volume":"13","author":"DJ Uhlenhopp","year":"2020","unstructured":"Uhlenhopp DJ, Then EO, Sunkara T, Gaduputi V. Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol. 2020;13:1010\u201321. https:\/\/doi.org\/10.1007\/s12328-020-01237-x.","journal-title":"Clin J Gastroenterol"},{"key":"3776_CR4","doi-asserted-by":"publisher","unstructured":"Fan N, Wang Z, Zhou C, Bludau M, Contino G, Zhao Y, et al. Comparison of outcomes between neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in patients with locally advanced esophageal cancer: a network meta-analysis. eClinicalMedicine. Elsevier; 2021;42. https:\/\/doi.org\/10.1016\/j.eclinm.2021.101183. Cited 2023 May 11.","DOI":"10.1016\/j.eclinm.2021.101183"},{"key":"3776_CR5","doi-asserted-by":"publisher","unstructured":"Ajani JA, D\u2019Amico TA, Bentrem DJ, Cooke D, Corvera C, Das P, et al. Esophageal and esophagogastric junction cancers, version 2.2023, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network. National Comprehensive Cancer Network; 2023;21:393-422. https:\/\/doi.org\/10.6004\/jnccn.2023.0019.","DOI":"10.6004\/jnccn.2023.0019"},{"key":"3776_CR6","doi-asserted-by":"publisher","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","volume":"30","author":"NM Anderson","year":"2020","unstructured":"Anderson NM, Simon MC. The tumor microenvironment. Curr Biol. 2020;30:R921\u20135. https:\/\/doi.org\/10.1016\/j.cub.2020.06.081.","journal-title":"Curr Biol"},{"key":"3776_CR7","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","volume":"41","author":"KE de Visser","year":"2023","unstructured":"de Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth. Cancer Cell. 2023;41:374\u2013403. https:\/\/doi.org\/10.1016\/j.ccell.2023.02.016.","journal-title":"Cancer Cell"},{"key":"3776_CR8","doi-asserted-by":"publisher","first-page":"100645","DOI":"10.1016\/j.drup.2019.100645","volume":"46","author":"YG Assaraf","year":"2019","unstructured":"Assaraf YG, Brozovic A, Gon\u00e7alves AC, Jurkovicova D, Lin\u0113 A, Machuqueiro M, et al. The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resist Updat. 2019;46:100645. https:\/\/doi.org\/10.1016\/j.drup.2019.100645.","journal-title":"Drug Resist Updat"},{"key":"3776_CR9","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s12943-022-01682-x","volume":"21","author":"P Nallasamy","year":"2022","unstructured":"Nallasamy P, Nimmakayala RK, Parte S, Are AC, Batra SK, Ponnusamy MP. Tumor microenvironment enriches the stemness features: the architectural event of therapy resistance and metastasis. Mol Cancer. 2022;21:225. https:\/\/doi.org\/10.1186\/s12943-022-01682-x.","journal-title":"Mol Cancer"},{"key":"3776_CR10","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41573-018-0004-1","volume":"18","author":"X Chen","year":"2019","unstructured":"Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discov. 2019;18:99\u2013115. https:\/\/doi.org\/10.1038\/s41573-018-0004-1.","journal-title":"Nat Rev Drug Discov"},{"key":"3776_CR11","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41575-019-0115-0","volume":"16","author":"H Kobayashi","year":"2019","unstructured":"Kobayashi H, Enomoto A, Woods SL, Burt AD, Takahashi M, Worthley DL. Cancer-associated fibroblasts in gastrointestinal cancer. Nat Rev Gastroenterol Hepatol. 2019;16:282\u201395. https:\/\/doi.org\/10.1038\/s41575-019-0115-0.","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"3776_CR12","doi-asserted-by":"publisher","first-page":"215860","DOI":"10.1016\/j.canlet.2022.215860","volume":"546","author":"L Qiu","year":"2022","unstructured":"Qiu L, Yue J, Ding L, Yin Z, Zhang K, Zhang H. Cancer-associated fibroblasts: an emerging target against esophageal squamous cell carcinoma. Cancer Lett. 2022;546:215860. https:\/\/doi.org\/10.1016\/j.canlet.2022.215860.","journal-title":"Cancer Lett"},{"key":"3776_CR13","doi-asserted-by":"publisher","first-page":"188598","DOI":"10.1016\/j.bbcan.2021.188598","volume":"1876","author":"R McShane","year":"2021","unstructured":"McShane R, Arya S, Stewart AJ, Caie PD, Bates M. Prognostic features of the tumour microenvironment in oesophageal adenocarcinoma. Biochim Biophys Acta Rev Cancer. 2021;1876:188598. https:\/\/doi.org\/10.1016\/j.bbcan.2021.188598.","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"3776_CR14","doi-asserted-by":"publisher","first-page":"11514","DOI":"10.1073\/pnas.94.21.11514","volume":"94","author":"MR Bootcov","year":"1997","unstructured":"Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-\u03b2 superfamily. Proc Natl Acad Sci U S A. 1997;94:11514\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3776_CR15","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1053\/gast.2002.32972","volume":"122","author":"K-S Kim","year":"2002","unstructured":"Kim K-S, Baek SJ, Flake GP, Loftin CD, Calvo BF, Eling TE. Expression and regulation of nonsteroidal anti-inflammatory drug-activated gene (NAG-1) in human and mouse tissue. Gastroenterology. 2002;122:1388\u201398. https:\/\/doi.org\/10.1053\/gast.2002.32972.","journal-title":"Gastroenterology"},{"key":"3776_CR16","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1111\/j.1474-9726.2010.00629.x","volume":"9","author":"FE Wiklund","year":"2010","unstructured":"Wiklund FE, Bennet AM, Magnusson PKE, Eriksson UK, Lindmark F, Wu L, et al. Macrophage inhibitory cytokine-1 (MIC-1\/GDF15): a new marker of all-cause mortality. Aging Cell. 2010;9:1057\u201364. https:\/\/doi.org\/10.1111\/j.1474-9726.2010.00629.x.","journal-title":"Aging Cell"},{"key":"3776_CR17","doi-asserted-by":"publisher","first-page":"e13168","DOI":"10.1111\/eci.13168","volume":"49","author":"H Arfsten","year":"2019","unstructured":"Arfsten H, Cho A, Freitag C, Raderer M, Goliasch G, Bartko PE, et al. GDF-15 in solid vs non-solid treatment-na\u00efve malignancies. Eur J Clin Invest. 2019;49:e13168. https:\/\/doi.org\/10.1111\/eci.13168.","journal-title":"Eur J Clin Invest"},{"key":"3776_CR18","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1038\/s41586-024-08305-z","volume":"637","author":"I Melero","year":"2025","unstructured":"Melero I, de Miguel LM, de Velasco G, Garralda E, Mart\u00edn-Liberal J, Joerger M, et al. Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours. Nature. 2025;637:1218\u201327. https:\/\/doi.org\/10.1038\/s41586-024-08305-z.","journal-title":"Nature"},{"key":"3776_CR19","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1038\/bjc.2015.100","volume":"112","author":"OM Fisher","year":"2015","unstructured":"Fisher OM, Levert-Mignon AJ, Lord SJ, Lee-Ng KKM, Botelho NK, Falkenback D, et al. MIC-1\/GDF15 in Barrett\u2019s oesophagus and oesophageal adenocarcinoma. Br J Cancer. 2015;112:1384\u201391. https:\/\/doi.org\/10.1038\/bjc.2015.100.","journal-title":"Br J Cancer"},{"key":"3776_CR20","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/sj.bjc.6605532","volume":"102","author":"RJE Skipworth","year":"2010","unstructured":"Skipworth RJE, Deans DaC, Tan BHL, Sangster K, Paterson-Brown S, Brown DA, et al. Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer. Br J Cancer. 2010;102:665\u201372. https:\/\/doi.org\/10.1038\/sj.bjc.6605532.","journal-title":"Br J Cancer"},{"key":"3776_CR21","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/s41578-021-00279-y","volume":"6","author":"M Hofer","year":"2021","unstructured":"Hofer M, Lutolf MP. Engineering organoids. Nat Rev Mater. 2021;6:402\u201320. https:\/\/doi.org\/10.1038\/s41578-021-00279-y.","journal-title":"Nat Rev Mater"},{"key":"3776_CR22","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41563-021-01057-5","volume":"21","author":"BL LeSavage","year":"2022","unstructured":"LeSavage BL, Suhar RA, Broguiere N, Lutolf MP, Heilshorn SC. Next-generation cancer organoids. Nat Mater. 2022;21:143\u201359. https:\/\/doi.org\/10.1038\/s41563-021-01057-5.","journal-title":"Nat Mater"},{"key":"3776_CR23","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","volume":"165","author":"H Clevers","year":"2016","unstructured":"Clevers H. Modeling development and disease with organoids. Cell. 2016;165:1586\u201397. https:\/\/doi.org\/10.1016\/j.cell.2016.05.082.","journal-title":"Cell"},{"key":"3776_CR24","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1038\/s41580-020-0259-3","volume":"21","author":"J Kim","year":"2020","unstructured":"Kim J, Koo B-K, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Biol. 2020;21:571\u201384. https:\/\/doi.org\/10.1038\/s41580-020-0259-3.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"3776_CR25","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.3390\/biomedicines11041058","volume":"11","author":"EM Tosca","year":"2023","unstructured":"Tosca EM, Ronchi D, Facciolo D, Magni P. Replacement, reduction, and refinement of animal experiments in anticancer drug development: the contribution of 3D in vitro cancer models in the drug efficacy assessment. Biomedicines. 2023;11:1058. https:\/\/doi.org\/10.3390\/biomedicines11041058.","journal-title":"Biomedicines"},{"key":"3776_CR26","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202202609","author":"W Li","year":"2023","unstructured":"Li W, Zhou Z, Zhou X, Khoo BL, Gunawan R, Chin YR, et al. 3D biomimetic models to reconstitute tumor microenvironment in vitro: spheroids, organoids, and tumor-on-a-chip. Adv Healthc Mater. 2023. https:\/\/doi.org\/10.1002\/adhm.202202609.","journal-title":"Adv Healthc Mater"},{"key":"3776_CR27","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s13045-020-00931-0","volume":"13","author":"M Zanoni","year":"2020","unstructured":"Zanoni M, Cortesi M, Zamagni A, Arienti C, Pignatta S, Tesei A. Modeling neoplastic disease with spheroids and organoids. J Hematol Oncol. 2020;13:97. https:\/\/doi.org\/10.1186\/s13045-020-00931-0.","journal-title":"J Hematol Oncol"},{"issue":"21","key":"3776_CR28","doi-asserted-by":"publisher","first-page":"7252","DOI":"10.1158\/1078-0432.CCR-04-0713","volume":"10","author":"RL Camp","year":"2004","unstructured":"Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252\u20139. https:\/\/doi.org\/10.1158\/1078-0432.CCR-04-0713.","journal-title":"Clin Cancer Res"},{"key":"3776_CR29","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1002\/1878-0261.12680","volume":"14","author":"M Kr\u00e4mer","year":"2020","unstructured":"Kr\u00e4mer M, Plum PS, Velazquez Camacho O, Folz-Donahue K, Thelen M, Garcia-Marquez I, et al. Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics. Mol Oncol. 2020;14:1170\u201384. https:\/\/doi.org\/10.1002\/1878-0261.12680.","journal-title":"Mol Oncol"},{"key":"3776_CR30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635.","journal-title":"Bioinformatics"},{"key":"3776_CR31","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8.","journal-title":"Genome Biol"},{"key":"3776_CR32","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1038\/nprot.2016.136","volume":"11","author":"S Tyanova","year":"2016","unstructured":"Tyanova S, Temu T, Cox J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat Protoc Nature Publishing Group. 2016;11:2301\u201319. https:\/\/doi.org\/10.1038\/nprot.2016.136.","journal-title":"Nat Protoc Nature Publishing Group"},{"key":"3776_CR33","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nprot.2017.147","volume":"13","author":"X Zhang","year":"2018","unstructured":"Zhang X, Smits AH, van Tilburg GB, Ovaa H, Huber W, Vermeulen M. Proteome-wide identification of ubiquitin interactions using UbIA-MS. Nat Protoc. 2018;13:530\u201350. https:\/\/doi.org\/10.1038\/nprot.2017.147.","journal-title":"Nat Protoc"},{"key":"3776_CR34","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","volume":"2","author":"E Cerami","year":"2012","unstructured":"Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401\u20134. https:\/\/doi.org\/10.1158\/2159-8290.CD-12-0095.","journal-title":"Cancer Discov"},{"key":"3776_CR35","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","volume":"41","author":"T Barrett","year":"2013","unstructured":"Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets\u2014update. Nucleic Acids Res. 2013;41:D991\u20135. https:\/\/doi.org\/10.1093\/nar\/gks1193.","journal-title":"Nucleic Acids Res"},{"key":"3776_CR36","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/1471-2407-13-137","volume":"13","author":"Q Wang","year":"2013","unstructured":"Wang Q, Ma C, Kemmner W. Wdr66 is a novel marker for risk stratification and involved in epithelial-mesenchymal transition of esophageal squamous cell carcinoma. BMC Cancer. 2013;13:137. https:\/\/doi.org\/10.1186\/1471-2407-13-137.","journal-title":"BMC Cancer"},{"key":"3776_CR37","doi-asserted-by":"publisher","first-page":"W242","DOI":"10.1093\/nar\/gkab418","volume":"49","author":"C Li","year":"2021","unstructured":"Li C, Tang Z, Zhang W, Ye Z, Liu F. GEPIA2021: integrating multiple deconvolution-based analysis into GEPIA. Nucleic Acids Res. 2021;49:W242\u20136. https:\/\/doi.org\/10.1093\/nar\/gkab418.","journal-title":"Nucleic Acids Res"},{"key":"3776_CR38","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41419-025-07773-z","volume":"16","author":"F Ju","year":"2025","unstructured":"Ju F, Weng J, Fan N, Wang Z, Zhou C, Zhao X, et al. AKR1C3 enhances radioresistance in esophageal adenocarcinoma via inhibiting ferroptosis through suppressing TRIM21-mediated ubiquitination of HSPA5. Cell Death Dis. 2025;16:483. https:\/\/doi.org\/10.1038\/s41419-025-07773-z.","journal-title":"Cell Death Dis"},{"key":"3776_CR39","doi-asserted-by":"publisher","unstructured":"Fan N, Raatz L, Chon S-H, Quaas A, Bruns C, Zhao Y. Subculture and cryopreservation of esophageal adenocarcinoma organoids: pros and cons for single cell digestion. JoVE (Journal of Visualized Experiments). 2022;e63281. https:\/\/doi.org\/10.3791\/63281.","DOI":"10.3791\/63281"},{"key":"3776_CR40","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s13045-021-01137-8","volume":"14","author":"H Hua","year":"2021","unstructured":"Hua H, Zhang H, Chen J, Wang J, Liu J, Jiang Y. Targeting Akt in cancer for precision therapy. J Hematol Oncol. 2021;14:128. https:\/\/doi.org\/10.1186\/s13045-021-01137-8.","journal-title":"J Hematol Oncol"},{"key":"3776_CR41","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.semcancer.2021.06.019","volume":"85","author":"L Yu","year":"2022","unstructured":"Yu L, Wei J, Liu P. Attacking the PI3K\/Akt\/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Semin Cancer Biol. 2022;85:69\u201394. https:\/\/doi.org\/10.1016\/j.semcancer.2021.06.019.","journal-title":"Semin Cancer Biol"},{"key":"3776_CR42","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12929-018-0468-7","volume":"25","author":"NP Lee","year":"2018","unstructured":"Lee NP, Chan CM, Tung LN, Wang HK, Law S. Tumor xenograft animal models for esophageal squamous cell carcinoma. J Biomed Sci. 2018;25:66. https:\/\/doi.org\/10.1186\/s12929-018-0468-7.","journal-title":"J Biomed Sci"},{"key":"3776_CR43","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/bs.enz.2019.10.003","volume":"46","author":"T Saito","year":"2019","unstructured":"Saito T, Ohashi S, Mizumoto A, Muto M. Patient-derived tumor models of esophageal cancer. Enzymes. 2019;46:97\u2013111. https:\/\/doi.org\/10.1016\/bs.enz.2019.10.003.","journal-title":"Enzymes"},{"key":"3776_CR44","doi-asserted-by":"publisher","unstructured":"Farin HF, Mosa MH, Ndreshkjana B, Grebbin BM, Ritter B, Menche C, et al. Colorectal cancer organoid-stroma biobank allows subtype-specific assessment of individualized therapy responses. Cancer Discov. 2023;CD-23-0050. https:\/\/doi.org\/10.1158\/2159-8290.CD-23-0050.","DOI":"10.1158\/2159-8290.CD-23-0050"},{"key":"3776_CR45","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1186\/s13046-022-02519-7","volume":"41","author":"S Schuth","year":"2022","unstructured":"Schuth S, Le Blanc S, Krieger TG, Jabs J, Schenk M, Giese NA, et al. Patient-specific modeling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system. J Exp Clin Cancer Res. 2022;41:312. https:\/\/doi.org\/10.1186\/s13046-022-02519-7.","journal-title":"J Exp Clin Cancer Res"},{"key":"3776_CR46","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.jcmgh.2020.09.003","volume":"11","author":"J Liu","year":"2021","unstructured":"Liu J, Li P, Wang L, Li M, Ge Z, Noordam L, et al. Cancer-associated fibroblasts provide a stromal niche for liver cancer organoids that confers trophic effects and therapy resistance. Cell Mol Gastroenterol Hepatol. 2021;11:407\u201331. https:\/\/doi.org\/10.1016\/j.jcmgh.2020.09.003.","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"3776_CR47","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s13046-016-0405-0","volume":"35","author":"Y Zhai","year":"2016","unstructured":"Zhai Y, Zhang J, Wang H, Lu W, Liu S, Yu Y, et al. Growth differentiation factor 15 contributes to cancer-associated fibroblasts-mediated chemo-protection of AML cells. J Exp Clin Cancer Res. 2016;35:147. https:\/\/doi.org\/10.1186\/s13046-016-0405-0.","journal-title":"J Exp Clin Cancer Res"},{"key":"3776_CR48","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1158\/0008-5472.CAN-13-2259","volume":"74","author":"F Bruzzese","year":"2014","unstructured":"Bruzzese F, H\u00e4ggl\u00f6f C, Leone A, Sj\u00f6berg E, Roca MS, Kiflemariam S, et al. Local and systemic protumorigenic effects of cancer-associated fibroblast-derived GDF15. Can Res. 2014;74:3408\u201317. https:\/\/doi.org\/10.1158\/0008-5472.CAN-13-2259.","journal-title":"Can Res"},{"issue":"8","key":"3776_CR49","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1158\/0008-5472.CAN-24-0086","volume":"84","author":"DJ Zabransky","year":"2024","unstructured":"Zabransky DJ, Chhabra Y, Fane ME, Kartalia E, Leatherman JM, H\u00fcser L, et al. Fibroblasts in the aged pancreas drive pancreatic cancer progression. Cancer Res. 2024;84(8):1221\u201336. https:\/\/doi.org\/10.1158\/0008-5472.CAN-24-0086.","journal-title":"Cancer Res"},{"key":"3776_CR50","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1073\/pnas.1820459116","volume":"116","author":"EA Ebbing","year":"2019","unstructured":"Ebbing EA, van der Zalm AP, Steins A, Creemers A, Hermsen S, Rentenaar R, et al. Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma. Proc Natl Acad Sci U S A. 2019;116:2237\u201342. https:\/\/doi.org\/10.1073\/pnas.1820459116.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"3776_CR51","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","volume":"20","author":"E Sahai","year":"2020","unstructured":"Sahai E, Astsaturov I, Cukierman E, DeNardo DG, Egeblad M, Evans RM, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20(3):174\u201386. https:\/\/doi.org\/10.1038\/s41568-019-0238-1.","journal-title":"Nat Rev Cancer"},{"key":"3776_CR52","doi-asserted-by":"publisher","first-page":"21304","DOI":"10.1038\/s41598-021-00706-8","volume":"11","author":"TA Karakasheva","year":"2021","unstructured":"Karakasheva TA, Gabre JT, Sachdeva UM, Cruz-Acu\u00f1a R, Lin EW, DeMarshall M, et al. Patient-derived organoids as a platform for modeling a patient\u2019s response to chemoradiotherapy in esophageal cancer. Sci Rep. 2021;11:21304. https:\/\/doi.org\/10.1038\/s41598-021-00706-8.","journal-title":"Sci Rep"},{"key":"3776_CR53","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s11684-022-0949-7","volume":"17","author":"Y Du","year":"2023","unstructured":"Du Y, Ma Y, Zhu Q, Fu Y, Li Y, Zhang Y, et al. GDF15 negatively regulates chemosensitivity via TGFBR2-AKT pathway-dependent metabolism in esophageal squamous cell carcinoma. Front Med. 2023;17:119\u201331. https:\/\/doi.org\/10.1007\/s11684-022-0949-7.","journal-title":"Front Med"},{"key":"3776_CR54","doi-asserted-by":"publisher","first-page":"e0187349","DOI":"10.1371\/journal.pone.0187349","volume":"12","author":"OE Olsen","year":"2017","unstructured":"Olsen OE, Skj\u00e6rvik A, St\u00f8rdal BF, Sundan A, Holien T. TGF-\u03b2 contamination of purified recombinant GDF15. PLoS ONE. 2017;12:e0187349. https:\/\/doi.org\/10.1371\/journal.pone.0187349.","journal-title":"PLoS ONE"},{"key":"3776_CR55","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1038\/nm.4392","volume":"23","author":"SE Mullican","year":"2017","unstructured":"Mullican SE, Lin-Schmidt X, Chin C-N, Chavez JA, Furman JL, Armstrong AA, et al. GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates. Nat Med Nature Publishing Group. 2017;23:1150\u20137. https:\/\/doi.org\/10.1038\/nm.4392.","journal-title":"Nat Med Nature Publishing Group"},{"key":"3776_CR56","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1038\/nm.4394","volume":"23","author":"L Yang","year":"2017","unstructured":"Yang L, Chang C-C, Sun Z, Madsen D, Zhu H, Padkj\u00e6r SB, et al. GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat Med Nature Publishing Group. 2017;23:1158\u201366. https:\/\/doi.org\/10.1038\/nm.4394.","journal-title":"Nat Med Nature Publishing Group"},{"key":"3776_CR57","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/s41419-018-0808-2","volume":"9","author":"Y Che","year":"2018","unstructured":"Che Y, Wang J, Li Y, Lu Z, Huang J, Sun S, et al. Cisplatin-activated PAI-1 secretion in the cancer-associated fibroblasts with paracrine effects promoting esophageal squamous cell carcinoma progression and causing chemoresistance. Cell Death Dis. 2018;9:759. https:\/\/doi.org\/10.1038\/s41419-018-0808-2.","journal-title":"Cell Death Dis"},{"key":"3776_CR58","doi-asserted-by":"publisher","first-page":"3689","DOI":"10.7150\/ijbs.62571","volume":"17","author":"Y Jin","year":"2021","unstructured":"Jin Y, Meng Q, Zhang B, Xie C, Chen X, Tian B, et al. Cancer-associated fibroblasts-derived exosomal miR-3656 promotes the development and progression of esophageal squamous cell carcinoma via the ACAP2\/PI3K-AKT signaling pathway. Int J Biol Sci. 2021;17:3689\u2013701. https:\/\/doi.org\/10.7150\/ijbs.62571.","journal-title":"Int J Biol Sci"},{"key":"3776_CR59","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/s41374-020-00512-2","volume":"101","author":"H Sakamoto","year":"2021","unstructured":"Sakamoto H, Koma Y-I, Higashino N, Kodama T, Tanigawa K, Shimizu M, et al. PAI-1 derived from cancer-associated fibroblasts in esophageal squamous cell carcinoma promotes the invasion of cancer cells and the migration of macrophages. Lab Invest. 2021;101:353\u201368. https:\/\/doi.org\/10.1038\/s41374-020-00512-2.","journal-title":"Lab Invest"},{"key":"3776_CR60","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/labinvest.2015.36","volume":"95","author":"N Urakawa","year":"2015","unstructured":"Urakawa N, Utsunomiya S, Nishio M, Shigeoka M, Takase N, Arai N, et al. GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways. Lab Invest. 2015;95:491\u2013503. https:\/\/doi.org\/10.1038\/labinvest.2015.36.","journal-title":"Lab Invest"},{"key":"3776_CR61","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1159\/000504394","volume":"87","author":"M Okamoto","year":"2020","unstructured":"Okamoto M, Koma YI, Kodama T, Nishio M, Shigeoka M, Yokozaki H. Growth differentiation factor 15 promotes progression of esophageal squamous cell carcinoma via TGF-\u03b2 Type II receptor activation. Pathobiology. 2020;87:100\u201313. https:\/\/doi.org\/10.1159\/000504394.","journal-title":"Pathobiology"},{"key":"3776_CR62","doi-asserted-by":"publisher","first-page":"e13013","DOI":"10.1111\/acel.13013","volume":"18","author":"Y Guo","year":"2019","unstructured":"Guo Y, Ayers JL, Carter KT, Wang T, Maden SK, Edmond D, et al. Senescence-associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15. Aging Cell. 2019;18:e13013. https:\/\/doi.org\/10.1111\/acel.13013.","journal-title":"Aging Cell"},{"key":"3776_CR63","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.cmet.2017.10.013","volume":"26","author":"C Bosc","year":"2017","unstructured":"Bosc C, Selak MA, Sarry J-E. Resistance is futile: targeting mitochondrial energetics and metabolism to overcome drug resistance in cancer treatment. Cell Metab. 2017;26:705\u20137. https:\/\/doi.org\/10.1016\/j.cmet.2017.10.013.","journal-title":"Cell Metab"},{"key":"3776_CR64","doi-asserted-by":"publisher","first-page":"3384","DOI":"10.3390\/ijms20143384","volume":"20","author":"V Cocetta","year":"2019","unstructured":"Cocetta V, Ragazzi E, Montopoli M. Mitochondrial involvement in cisplatin resistance. Int J Mol Sci. 2019;20:3384. https:\/\/doi.org\/10.3390\/ijms20143384.","journal-title":"Int J Mol Sci"},{"key":"3776_CR65","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/path.4199","volume":"230","author":"M Aichler","year":"2013","unstructured":"Aichler M, Elsner M, Ludyga N, Feuchtinger A, Zangen V, Maier SK, et al. Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria. J Pathol. 2013;230:410\u20139. https:\/\/doi.org\/10.1002\/path.4199.","journal-title":"J Pathol"},{"key":"3776_CR66","doi-asserted-by":"publisher","first-page":"100802","DOI":"10.1016\/j.xcrm.2022.100802","volume":"3","author":"MPG Dings","year":"2022","unstructured":"Dings MPG, van der Zalm AP, Bootsma S, van Maanen TFJ, Waasdorp C, van den Ende T, et al. Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer. Cell Rep Med. 2022;3:100802. https:\/\/doi.org\/10.1016\/j.xcrm.2022.100802.","journal-title":"Cell Rep Med"},{"issue":"11","key":"3776_CR67","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1038\/sj.cdd.4400740","volume":"7","author":"JA S\u00e1nchez-Alc\u00e1zar","year":"2000","unstructured":"S\u00e1nchez-Alc\u00e1zar JA, Ault JG, Khodjakov A, Schneider E. Increased mitochondrial cytochrome c levels and mitochondrial hyperpolarization precede camptothecin-induced apoptosis in Jurkat cells. Cell Death Differ. 2000;7(11):1090\u2013100. https:\/\/doi.org\/10.1038\/sj.cdd.4400740.","journal-title":"Cell Death Differ"},{"issue":"11","key":"3776_CR68","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/s41419-019-2081-4","volume":"10","author":"M Kleih","year":"2019","unstructured":"Kleih M, B\u00f6pple K, Dong M, Gai\u00dfler A, Heine S, Olayioye MA, et al. Direct impact of cisplatin on mitochondria induces ROS production that dictates cell fate of ovarian cancer cells. Cell Death Dis. 2019;10(11):851. https:\/\/doi.org\/10.1038\/s41419-019-2081-4.","journal-title":"Cell Death Dis"},{"issue":"45","key":"3776_CR69","doi-asserted-by":"publisher","first-page":"43377","DOI":"10.1074\/jbc.M206373200","volume":"277","author":"G Nowak","year":"2002","unstructured":"Nowak G. Protein kinase C-alpha and ERK1\/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells. J Biol Chem. 2002;277(45):43377\u201388. https:\/\/doi.org\/10.1074\/jbc.M206373200.","journal-title":"J Biol Chem"},{"key":"3776_CR70","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s00281-020-00813-0","volume":"42","author":"M Conte","year":"2020","unstructured":"Conte M, Martucci M, Chiariello A, Franceschi C, Salvioli S. Mitochondria, immunosenescence and inflammaging: a role for mitokines? Semin Immunopathol. 2020;42:607\u201317. https:\/\/doi.org\/10.1007\/s00281-020-00813-0.","journal-title":"Semin Immunopathol"},{"key":"3776_CR71","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1007\/s00018-020-03748-9","volume":"78","author":"S Klaus","year":"2021","unstructured":"Klaus S, Igual Gil C, Ost M. Regulation of diurnal energy balance by mitokines. Cell Mol Life Sci. 2021;78:3369\u201384. https:\/\/doi.org\/10.1007\/s00018-020-03748-9.","journal-title":"Cell Mol Life Sci"},{"key":"3776_CR72","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.cmet.2017.07.007","volume":"26","author":"NA Khan","year":"2017","unstructured":"Khan NA, Nikkanen J, Yatsuga S, Jackson C, Wang L, Pradhan S, et al. MTORC1 regulates mitochondrial integrated stress response and mitochondrial myopathy progression. Cell Metab. 2017;26:419-428.e5. https:\/\/doi.org\/10.1016\/j.cmet.2017.07.007.","journal-title":"Cell Metab"},{"key":"3776_CR73","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1002\/art.42033","volume":"74","author":"X Zhou","year":"2022","unstructured":"Zhou X, Trinh-Minh T, Tran-Manh C, Gie\u00dfl A, Bergmann C, Gy\u00f6rfi A-H, et al. Impaired mitochondrial transcription factor a expression promotes mitochondrial damage to drive fibroblast activation and fibrosis in systemic sclerosis. Arthritis Rheumatol. 2022;74:871\u201381. https:\/\/doi.org\/10.1002\/art.42033.","journal-title":"Arthritis Rheumatol"},{"key":"3776_CR74","doi-asserted-by":"publisher","first-page":"e13752","DOI":"10.1111\/acel.13752","volume":"22","author":"S Wedel","year":"2023","unstructured":"Wedel S, Martic I, Guerrero Navarro L, Ploner C, Pierer G, Jansen-D\u00fcrr P, et al. Depletion of growth differentiation factor 15 (GDF15) leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts. Aging Cell. 2023;22:e13752. https:\/\/doi.org\/10.1111\/acel.13752.","journal-title":"Aging Cell"},{"key":"3776_CR75","doi-asserted-by":"publisher","first-page":"0901","DOI":"10.34133\/research.0901","volume":"8","author":"Z Zhao","year":"2025","unstructured":"Zhao Z, Cai H, Zhao Z, Wang X, Nie W, Zhao F, et al. Cancer-Associated Fibroblast-Derived GDF15 Induces Oxidative Stress and Neutrophil Infiltration in Head and Neck Squamous Cell Carcinoma through the PI3K\/AKT\/STAT3 Axis Cascade. Research (Wash D C). 2025;8:0901. https:\/\/doi.org\/10.34133\/research.0901.","journal-title":"Research (Wash D C)."},{"key":"3776_CR76","doi-asserted-by":"publisher","first-page":"102322","DOI":"10.1016\/j.redox.2022.102322","volume":"52","author":"Y Wang","year":"2022","unstructured":"Wang Y, Chen C, Chen J, Sang T, Peng H, Lin X, et al. Overexpression of NAG-1\/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation. Redox Biol. 2022;52:102322. https:\/\/doi.org\/10.1016\/j.redox.2022.102322.","journal-title":"Redox Biol"},{"key":"3776_CR77","doi-asserted-by":"publisher","first-page":"6047","DOI":"10.7314\/apjcp.2014.15.15.6047","volume":"15","author":"Z-H Lu","year":"2014","unstructured":"Lu Z-H, Yang L, Yu J-W, Lu M, Li J, Zhou J, et al. Weight loss correlates with macrophage inhibitory cytokine-1 expression and might influence outcome in patients with advanced esophageal squamous cell carcinoma. Asian Pac J Cancer Prev. 2014;15:6047\u201352. https:\/\/doi.org\/10.7314\/apjcp.2014.15.15.6047.","journal-title":"Asian Pac J Cancer Prev"},{"key":"3776_CR78","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/cas.12331","volume":"105","author":"XB Wang","year":"2014","unstructured":"Wang XB, Jiang XR, Yu XY, Wang L, He S, Feng FY, et al. Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy. Cancer Sci. 2014;105:176\u201385. https:\/\/doi.org\/10.1111\/cas.12331.","journal-title":"Cancer Sci"},{"key":"3776_CR79","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1146\/annurev-physiol-022020-045449","volume":"83","author":"SN Breit","year":"2021","unstructured":"Breit SN, Brown DA, Tsai VW-W. The GDF15-GFRAL pathway in health and metabolic disease: friend or foe? Annu Rev Physiol. 2021;83:127\u201351. https:\/\/doi.org\/10.1146\/annurev-physiol-022020-045449.","journal-title":"Annu Rev Physiol"},{"key":"3776_CR80","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.cmet.2018.07.018","volume":"28","author":"VWW Tsai","year":"2018","unstructured":"Tsai VWW, Husaini Y, Sainsbury A, Brown DA, Breit SN. The MIC-1\/GDF15-GFRAL pathway in energy homeostasis: implications for obesity, cachexia, and other associated diseases. Cell Metab. 2018;28:353\u201368. https:\/\/doi.org\/10.1016\/j.cmet.2018.07.018.","journal-title":"Cell Metab"},{"issue":"6","key":"3776_CR81","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.cmet.2020.10.023","volume":"32","author":"DM Breen","year":"2020","unstructured":"Breen DM, Kim H, Bennett D, Calle RA, Collins S, Esquejo RM, et al. GDF-15 neutralization alleviates platinum-based chemotherapy-induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates. Cell Metab. 2020;32(6):938-950.e6. https:\/\/doi.org\/10.1016\/j.cmet.2020.10.023.","journal-title":"Cell Metab"},{"key":"3776_CR82","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1016\/j.cell.2023.03.016","volume":"186","author":"Y Chhabra","year":"2023","unstructured":"Chhabra Y, Weeraratna AT. Fibroblasts in cancer: unity in heterogeneity. Cell. 2023;186:1580\u2013609. https:\/\/doi.org\/10.1016\/j.cell.2023.03.016.","journal-title":"Cell"},{"key":"3776_CR83","doi-asserted-by":"publisher","first-page":"CT108","DOI":"10.1158\/1538-7445.AM2023-CT108","volume":"83","author":"J Crawford","year":"2023","unstructured":"Crawford J, Calle RA, Collins SM, Weng Y, Lubaczewski SL, Buckeridge C, et al. Abstract CT108: first-in-patient study of the GDF-15 inhibitor ponsegromab in patients with cancer and cachexia: safety, tolerability, and exploratory measures of efficacy. Cancer Res. 2023;83:CT108. https:\/\/doi.org\/10.1158\/1538-7445.AM2023-CT108.","journal-title":"Cancer Res"},{"key":"3776_CR84","doi-asserted-by":"publisher","unstructured":"Melero I, Calvo E, Goebeler M-E, Garralda E, Dummer R, Rodr\u00edguez-Ruiz M, et al. 504 A phase I, first-in-human clinical trial of the GDF-15 neutralizing antibody CTL-002 in subjects with advanced stage solid tumors (Acronym: GDFATHER). J Immunother Cancer. BMJ Specialist Journals; 2021;9. https:\/\/doi.org\/10.1136\/jitc-2021-SITC2021.504. Cited 2023 July 31.","DOI":"10.1136\/jitc-2021-SITC2021.504"}],"updated-by":[{"DOI":"10.1186\/s13046-026-03859-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T00:00:00Z","timestamp":1793923200000}}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-026-03776-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-026-03776-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-026-03776-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T07:53:02Z","timestamp":1794297182000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-026-03776-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3776"],"URL":"https:\/\/doi.org\/10.1186\/s13046-026-03776-6","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"9 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised: error was found in Fig. 3K the representative flow cytometry image for Group OE19 sh# + 50ng\/ml rGDF15 was mistakenly duplicated with the image from Group OE19 sh#.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2026","order":9,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":10,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13046-026-03859-4","URL":"https:\/\/doi.org\/10.1186\/s13046-026-03859-4","order":12,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The utilization of patients' materials from the Department of General, Visceral, Thoracic, and Transplant Surgery at the University Hospital of Cologne was conducted under the approval of BioMaSOTA, as granted by the Ethics Committee of the University of Cologne (ID: 13\u2013091) and the study related utilization (ID:18\u2013274). All patient materials were collected after obtaining informed consent.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"164"}}