{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:07:18Z","timestamp":1789978038243,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>PTTG1 has been implicated in tumor progression and drug resistance, but its role in acquired anlotinib resistance in non\u2010small cell lung cancer (NSCLC) remains unclear. This study investigated whether PTTG1 contributes to resistance and immune remodeling in NSCLC. We analyzed peripheral blood from NSCLC patients collected before treatment, during response, and after acquired resistance to define clinical changes associated with anlotinib failure. Anlotinib\u2010resistant A549\/AL and NCI\u2010H1975\/AL cell models were established and subjected to lentiviral shRNA\u2010mediated PTTG1 silencing to assess tumor\u2010intrinsic functions and drug sensitivity. Tumor cell proliferation, migration, invasion, and molecular changes were evaluated using CCK\u20108, EdU, Transwell, reverse transcription quantitative polymerase chain reaction, Western blotting, immunofluorescence, immunohistochemistry, co\u2010immunoprecipitation, STRING analysis, and humanized mouse models. Immune remodeling was assessed by flow cytometry in PBMC co\u2010culture and tumor samples to examine T\u2010cell subsets and cytotoxic effector activity. PTTG1 was upregulated in resistant clinical samples and resistant NSCLC cell models. Silencing PTTG1 suppressed proliferation, migration, invasion, epithelial\u2010mesenchymal transition, tumor growth and metastasis in\u00a0vivo, with enhanced anlotinib efficacy observed in subcutaneous xenografts. PTTG1 knockdown reprogrammed the tumor immune microenvironment (experimental models) toward an activated cytotoxic state, characterized by increased CD8+ T\u2010cell infiltration and enhanced cytotoxic effector activity, with reduction of immune checkpoint\u2010associated suppression. Mechanistically, STRING analysis and co\u2010immunoprecipitation identified AURKA as a direct PTTG1\u2010interacting protein, and AURKA overexpression reversed the immune\u2010activating effects of PTTG1 depletion. In conclusion, PTTG1 promotes acquired anlotinib resistance in NSCLC by coupling malignant progression with immune suppression via the PTTG1\u2010AURKA axis. Targeting PTTG1 may be a strategy to overcome resistance and restore anti\u2010tumor immunity.<\/jats:p>","DOI":"10.1002\/biof.70153","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:55:01Z","timestamp":1789977301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>PTTG1<\/scp>\n                    \/\n                    <scp>AURKA<\/scp>\n                    Axis Drives Acquired Anlotinib Resistance in Non\u2010Small Cell Lung Cancer by Remodeling the Tumor Immune Microenvironment"],"prefix":"10.1002","volume":"52","author":[{"given":"Kaiyuan","family":"Hui","sequence":"first","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology Lianyungang Clinical College of Nanjing Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4646-2055","authenticated-orcid":false,"given":"Xiaodong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology The Affiliated Lianyungang Hospital of Xuzhou Medical University  Lianyungang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/cac2.12505","article-title":"Management of Locally Advanced Non\u2010Small Cell Lung Cancer: State of the Art and Future Directions","volume":"44","author":"Miao D.","year":"2024","journal-title":"Cancer Communications"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.stem.2024.03.008","article-title":"Patient\u2010Derived Tumor\u2010Like Cell Clusters for Personalized Chemo\u2010 and Immunotherapies in Non\u2010Small Cell Lung Cancer","volume":"31","author":"Yin S.","year":"2024","journal-title":"Cell Stem Cell"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2024.102724","article-title":"Neoadjuvant EGFR\u2010TKI Therapy in Non\u2010Small Cell Lung Cancer","volume":"126","author":"Grant 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