{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T21:09:00Z","timestamp":1787432940803,"version":"build-2736575974"},"reference-count":69,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Internal Medicine II, Medical Center\u2014University of Freiburg and Medical Faculty"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["413517907"],"award-info":[{"award-number":["413517907"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrial carcinoma (EC) is the most common malignancy of the female reproductive tract, with increasing incidence driven by aging populations and obesity. While molecular classification has improved diagnostic precision, the identification of clinically relevant metabolic biomarkers remains incomplete, and targeted therapies are not yet standardized. In this study, we investigated metabolic alterations in four EC cell lines (AN3-CA, EFE-184, HEC-1B and MFE-296) compared to non-malignant controls under normoxic and stress conditions (hypoxia and lactic acidosis) to identify metabolomic differences with potential clinical relevance. Untargeted gas chromatography\u2013mass spectrometry (GC\/MS) and targeted liquid chromatography\u2013mass spectrometry (LC\/MS) profiling revealed two distinct metabolic subtypes of EC. Cells of metabolic subtype 1 (AN3-CA and EFE-184) exhibited high biosynthetic and energy demands, enhanced cholesterol and hexosyl-ceramides synthesis and increased RNA stability, consistent with classical cancer-associated metabolic reprogramming. Cells of metabolic subtype 2 (HEC-1B and MFE-296) displayed a phospholipid-dominant metabolic profile and greater hypoxia tolerance, suggesting enhanced tumor aggressiveness and metastatic potential. Key metabolic findings were validated via real-time quantitative PCR. This study identifies and characterizes distinct metabolic subtypes of EC within the investigated cancer cell lines, thereby contributing to a better understanding of tumor heterogeneity. The results provide a basis for potential diagnostic differentiation based on specific metabolic profiles and may support the identification of novel therapeutic targets. Further validation in three-dimensional culture models and ultimately patient-derived samples is required to assess clinical relevance and integration with current molecular classifications.<\/jats:p>","DOI":"10.3390\/ijms26199573","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T16:43:54Z","timestamp":1759250634000},"page":"9573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling Metabolic Subtypes in Endometrial Cancer Cell Lines: Insights from Metabolomic Analysis Under Standard and Stress Conditions"],"prefix":"10.3390","volume":"26","author":[{"given":"Lana","family":"McCaslin","sequence":"first","affiliation":[{"name":"Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine\u2014University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-1781","authenticated-orcid":false,"given":"Simon","family":"Lagies","sequence":"additional","affiliation":[{"name":"Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-4946","authenticated-orcid":false,"given":"Daniel A.","family":"Mohl","sequence":"additional","affiliation":[{"name":"Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar A.","family":"Plattner","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine\u2014University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"N\u00f6thling","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine\u2014University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias C.","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine\u2014University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-6490","authenticated-orcid":false,"given":"Ingolf","family":"Juhasz-B\u00f6ss","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine\u2014University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kammerer","sequence":"additional","affiliation":[{"name":"Core Competence Metabolomics, Hilde-Mangold-Haus, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Signaling Research Centre BIOSS, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-5547","authenticated-orcid":false,"given":"Clara","family":"Backhaus","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Medical Center and Faculty of Medicine\u2014University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Makker, V., MacKay, H., Ray-Coquard, I., Levine, D.A., Westin, S.N., Aoki, D., and Oaknin, A. 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