Yibo Guo, Mingtao Chen, Jie Yang, Wenkai Zhou, Guanying Feng, Yang Wang, Tong Ji, Yu Zhang, Zheqi Liu
{"title":"CAF 分泌的 COL5A2 激活 PI3K/AKT 通路,介导头颈部鳞状细胞癌的厄洛替尼耐药性","authors":"Yibo Guo, Mingtao Chen, Jie Yang, Wenkai Zhou, Guanying Feng, Yang Wang, Tong Ji, Yu Zhang, Zheqi Liu","doi":"10.1111/odi.15130","DOIUrl":null,"url":null,"abstract":"ObjectiveTo investigate the mechanisms behind acquired resistance to erlotinib in head and neck squamous cell carcinoma (HNSCC) with a focus on the role of cancer‐associated fibroblasts (CAFs) and the PI3K/AKT signaling pathway.Materials and MethodsThis study analyzed gene expression profiles of erlotinib‐sensitive and ‐resistant HNSCC cell lines using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. It included microarray and RNA‐sequencing data, differentially expressed genes (DEGs) analysis, and pathway enrichment. In vitro experiments assessed the functional role of CAFs and the impact of the extracellular matrix component COL5A2 on erlotinib resistance.ResultsWe identified 124 DEGs associated with erlotinib resistance, with key genes like COL5A2 significantly upregulated. CAFs were found to highly express COL5A2, enhancing erlotinib resistance by activating the PI3K/AKT pathway. Higher erlotinib resistance scores correlated with increased infiltration of CAFs.ConclusionsErlotinib resistance in HNSCC is significantly influenced by the tumor microenvironment (TME), particularly through CAFs and the PI3K/AKT pathway. Targeting these mechanisms may offer new therapeutic strategies to overcome resistance in HNSCC patients.","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CAF‐secreted COL5A2 activates the PI3K/AKT pathway to mediate erlotinib resistance in head and neck squamous cell carcinoma\",\"authors\":\"Yibo Guo, Mingtao Chen, Jie Yang, Wenkai Zhou, Guanying Feng, Yang Wang, Tong Ji, Yu Zhang, Zheqi Liu\",\"doi\":\"10.1111/odi.15130\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"ObjectiveTo investigate the mechanisms behind acquired resistance to erlotinib in head and neck squamous cell carcinoma (HNSCC) with a focus on the role of cancer‐associated fibroblasts (CAFs) and the PI3K/AKT signaling pathway.Materials and MethodsThis study analyzed gene expression profiles of erlotinib‐sensitive and ‐resistant HNSCC cell lines using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. It included microarray and RNA‐sequencing data, differentially expressed genes (DEGs) analysis, and pathway enrichment. In vitro experiments assessed the functional role of CAFs and the impact of the extracellular matrix component COL5A2 on erlotinib resistance.ResultsWe identified 124 DEGs associated with erlotinib resistance, with key genes like COL5A2 significantly upregulated. CAFs were found to highly express COL5A2, enhancing erlotinib resistance by activating the PI3K/AKT pathway. Higher erlotinib resistance scores correlated with increased infiltration of CAFs.ConclusionsErlotinib resistance in HNSCC is significantly influenced by the tumor microenvironment (TME), particularly through CAFs and the PI3K/AKT pathway. Targeting these mechanisms may offer new therapeutic strategies to overcome resistance in HNSCC patients.\",\"PeriodicalId\":19615,\"journal\":{\"name\":\"Oral diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-09-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oral diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/odi.15130\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oral diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/odi.15130","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
CAF‐secreted COL5A2 activates the PI3K/AKT pathway to mediate erlotinib resistance in head and neck squamous cell carcinoma
ObjectiveTo investigate the mechanisms behind acquired resistance to erlotinib in head and neck squamous cell carcinoma (HNSCC) with a focus on the role of cancer‐associated fibroblasts (CAFs) and the PI3K/AKT signaling pathway.Materials and MethodsThis study analyzed gene expression profiles of erlotinib‐sensitive and ‐resistant HNSCC cell lines using datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. It included microarray and RNA‐sequencing data, differentially expressed genes (DEGs) analysis, and pathway enrichment. In vitro experiments assessed the functional role of CAFs and the impact of the extracellular matrix component COL5A2 on erlotinib resistance.ResultsWe identified 124 DEGs associated with erlotinib resistance, with key genes like COL5A2 significantly upregulated. CAFs were found to highly express COL5A2, enhancing erlotinib resistance by activating the PI3K/AKT pathway. Higher erlotinib resistance scores correlated with increased infiltration of CAFs.ConclusionsErlotinib resistance in HNSCC is significantly influenced by the tumor microenvironment (TME), particularly through CAFs and the PI3K/AKT pathway. Targeting these mechanisms may offer new therapeutic strategies to overcome resistance in HNSCC patients.
期刊介绍:
Oral Diseases is a multidisciplinary and international journal with a focus on head and neck disorders, edited by leaders in the field, Professor Giovanni Lodi (Editor-in-Chief, Milan, Italy), Professor Stefano Petti (Deputy Editor, Rome, Italy) and Associate Professor Gulshan Sunavala-Dossabhoy (Deputy Editor, Shreveport, LA, USA). The journal is pre-eminent in oral medicine. Oral Diseases specifically strives to link often-isolated areas of dentistry and medicine through broad-based scholarship that includes well-designed and controlled clinical research, analytical epidemiology, and the translation of basic science in pre-clinical studies. The journal typically publishes articles relevant to many related medical specialties including especially dermatology, gastroenterology, hematology, immunology, infectious diseases, neuropsychiatry, oncology and otolaryngology. The essential requirement is that all submitted research is hypothesis-driven, with significant positive and negative results both welcomed. Equal publication emphasis is placed on etiology, pathogenesis, diagnosis, prevention and treatment.