{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:30:10Z","timestamp":1793305810344,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T00:00:00Z","timestamp":1745280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972552"],"award-info":[{"award-number":["81972552"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273201"],"award-info":[{"award-number":["82273201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RNA-binding proteins (RBPs) critically regulate post-transcriptional gene networks, yet their roles and mechanisms in oral squamous cell carcinoma (OSCC) remain underexplored. Dysregulated RBPs were identified through integrated analysis of RNA-seq and single-cell RNA-seq. The oncogenic functions of IGF2BP2 were evaluated through tissue microarrays, CCK-8, transwell assays, mouse xenografts, and Igf2bp2-deficient mouse models of tongue SCC (TSCC). Subsequently, we utilized RNA-seq, RIP-seq, RIP\/MeRIP-qPCR, and dual-luciferase reporter assays to investigate IGF2BP2-target genes. Furthermore, cell co-culture system and mouse TSCC models were used to validate the therapeutic effect of the IGF2BP2 inhibitor. IGF2BP2 was the most markedly upregulated RBP in OSCC cells and cancer-associated fibroblasts (CAFs), correlating with unfavorable prognosis. IGF2BP2 deprivation significantly impaired human OSCC proliferation and metastasis, and delayed mouse TSCC onset. Mechanistically, IGF2BP2 stabilized EGFR and PIK3R1 mRNA via m6A-dependent interactions, thereby sustaining activation of the EGFR\/PI3K\/AKT oncogenic axis. Pharmacological inhibition of IGF2BP2 exhibited anti-OSCC efficacy in vivo and in vitro by concurrently suppressing EGFR and PI3K\/AKT pathway activity, overcoming anti-EGFR resistance resulting from cell-intrinsic PI3K\/AKT hyperactivation and CAF-secreted factors. Our findings identified IGF2BP2 as a master regulator of OSCC progression and a promising therapeutic target, offering an alternative strategy for OSCC patients suffering anti-EGFR resistance.<\/jats:p>","DOI":"10.3390\/ijms26093941","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T20:24:52Z","timestamp":1745353492000},"page":"3941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dual Disruption of EGFR\/PI3K Signaling: IGF2BP2 Targeting Reverses Anti-EGFR Resistance in CAFs-Infiltrated Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"given":"Yaying","family":"Hu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"},{"name":"Department of Oral Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshuang","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"},{"name":"Department of Oral Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Nong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"},{"name":"Department of Oral Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"},{"name":"Department of Oral Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, 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China"},{"name":"Department of Oral Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0965-3027","authenticated-orcid":false,"given":"Jiali","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China"},{"name":"Department of Oral Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/nsmb.2638","article-title":"The RNA-binding protein repertoire of embryonic stem 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