{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:17:17Z","timestamp":1788455837015,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation of China","doi-asserted-by":"publisher","award":["LQ23H160002"],"award-info":[{"award-number":["LQ23H160002"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"award":["LQ23H160002"],"award-info":[{"award-number":["LQ23H160002"]}],"id":[{"id":"https:\/\/ror.org\/04aqat463","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Innovation Guidance Special Program for New-type Research and Development Institutions in Jiaxing","award":["2025YDZX028"],"award-info":[{"award-number":["2025YDZX028"]}]},{"name":"the fund of Yangtze Delta Region Institute of Tsinghua University, Zhejiang","award":["LZZLX23C002"],"award-info":[{"award-number":["LZZLX23C002"]}]},{"name":"the Collaborative Project with China Resources Research Institute of Science & Technology","award":["ILH24001"],"award-info":[{"award-number":["ILH24001"]}]},{"name":"the Key Research and Development Program of Shihezi City","award":["2024SF08"],"award-info":[{"award-number":["2024SF08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>KRAS G12C mutation is a clinically relevant driver in non-small cell lung cancer (NSCLC), yet the signaling networks that modulate malignant behavior in this context remain incompletely defined. In this study, we examined the functional role of FOXD3 and its relationship with NF-\u03baB signaling in KRAS G12C-mutant NSCLC models. Stable FOXD3 overexpression was established in SW1573 and LU65 cells. FOXD3 reduced cell viability, migration, and invasion while increasing caspase 3\/7 activity in both cell lines. Transcriptomic profiling in LU65 cells followed by Hallmark enrichment analysis identified TNF\u03b1 signaling via NF-\u03baB as a prominently altered pathway associated with FOXD3 overexpression. Consistently, NF-\u03baB dual-luciferase assays showed reduced basal NF-\u03baB transcriptional activity in FOXD3-overexpressing cells. TNF\u03b1 stimulation partially reversed the inhibitory effects of FOXD3 on proliferation, migration, and invasion and attenuated FOXD3-induced apoptosis. In addition, stable FOXD3 overexpression suppressed xenograft growth in vivo. Collectively, these findings support a functional association between FOXD3 overexpression and reduced NF-\u03baB-related transcriptional activity in KRAS G12C-mutant NSCLC models, although the present data do not establish direct causal mediation by NF-\u03baB.<\/jats:p>","DOI":"10.3390\/cells15171564","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"1564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FOXD3 Is Functionally Linked to NF-\u03baB Signaling in KRAS G12C-Mutant NSCLC Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Pengzhen","family":"Xu","sequence":"first","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"},{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Women\u2019s Hospital, School of Medicine, Zhejiang University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Guo","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Qingdao Academy, Qingdao 266111, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Cao","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6166-1484","authenticated-orcid":false,"given":"Qing","family":"Sheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4257-0100","authenticated-orcid":false,"given":"Wenfei","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"},{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China"},{"name":"Zhejiang Key Laboratory of Multiomics and Molecular Enzymology, Yangtze Delta Region Institute of Tsinghua University, Zhejiang, Jiaxing 314006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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