CAF‐secreted COL5A2 activates the PI3K/AKT pathway to mediate erlotinib resistance in head and neck squamous cell carcinoma

IF 2.9 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Oral diseases Pub Date : 2024-09-17 DOI:10.1111/odi.15130

Yibo Guo, Mingtao Chen, Jie Yang, Wenkai Zhou, Guanying Feng, Yang Wang, Tong Ji, Yu Zhang, Zheqi Liu

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引用次数: 0

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.

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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

材料与方法本研究利用基因表达总库（GEO）和癌症基因组图谱（TCGA）数据库中的数据集，分析了厄洛替尼敏感和耐药 HNSCC 细胞系的基因表达谱。它包括微阵列和 RNA 序列数据、差异表达基因 (DEG) 分析和通路富集。体外实验评估了CAFs的功能作用以及细胞外基质成分COL5A2对厄洛替尼耐药的影响。结果我们发现了124个与厄洛替尼耐药相关的DEGs，其中COL5A2等关键基因显著上调。研究发现，CAFs高表达COL5A2，通过激活PI3K/AKT通路增强厄洛替尼耐药性。结论HNSCC的厄洛替尼耐药性受肿瘤微环境（TME）的显著影响，尤其是通过CAFs和PI3K/AKT通路。针对这些机制可能为克服 HNSCC 患者的耐药性提供新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oral diseases 医学-牙科与口腔外科

CiteScore

7.60

自引率

5.30%

发文量

325

审稿时长

4-8 weeks

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.

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