{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:38:04Z","timestamp":1793086684747,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The disease course in patients with advanced lung cancer with malignant serous effusions (ALC\u2010MSE) is complex, and treatment outcomes are difficult to predict; systematic studies on the tumor stem cell\u2010like characteristics and regulatory mechanisms of this condition are still lacking. Based on single\u2010cell transcriptomic data and the TCGA\u2010LUAD cohort, this study systematically analyzed the functional characteristics and key regulatory networks of malignant epithelial cells in severe lung cancer. Key findings include: epithelial cells in severe lung cancer exhibit significantly attenuated inflammation\u2010 and immunity\u2010related signaling pathways (including NF\u2010\u03baB, TNF, and JAK\u2013STAT signaling pathways), enhanced stem cell\u2010like properties, and metabolic reprogramming; we identified a highly stem\u2010like malignant epithelial cell subpopulation, represented by Cluster 3, which is enriched in stem\u2010like pathways such as Notch, Hippo, TGF\u2010\u03b2, and FoxO, and is accompanied by enhanced mitochondrial metabolism and stress adaptability; STMN1 is a key molecule regulating this stem\u2010like state, showing a significant positive correlation with stemness scores and mRNAi; cells with high STMN1 expression gain a survival advantage and may maintain their stemness by attenuating CAF\/ECM signaling with other cells (COL1A1\u2010CD44), inhibiting complement activation and antigen presentation signaling (such as C3, ANXA1, and MHC\u2010II\u2010related molecules), and enhancing stemness niche signaling (MIF\u2010CD74\/CD44). Furthermore, NELFE, MYBL2, FOXN3, POLR2A, and RAD21 were identified as potential upstream regulators of STMN1. In\u00a0vitro experiments confirmed that, following induction of stem cell\u2010like properties, STMN1 was significantly overexpressed in lung adenocarcinoma cells, accompanied by upregulation of related stem cell markers (SOX2, NANOG, OCT4, and CD44). In summary, this study reveals a significantly enhanced stemness state in malignant epithelial cells in advanced lung cancer, accompanied by suppressed inflammatory signaling and enhanced metabolic adaptation, and identifies STMN1 as a key molecule driving stemness maintenance and disease progression.<\/jats:p>","DOI":"10.1111\/cbdd.70420","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:43:14Z","timestamp":1792582994000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Dissection of Inflammatory Suppression and Stemness Plasticity Reveals STMN1\u2010Associated Malignant Epithelial Cells in Severe Lung Cancer"],"prefix":"10.1111","volume":"108","author":[{"given":"Yanmei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology The Affiliated Yongchuan Hospital of Chongqing Medical University  Chongqing 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