EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression
Objectives Hypopharyngeal cancer (HPC), originating from the hypopharyngeal mucosa, is associated with a poor prognosis. Extracellular matrix (ECM) stiffness is closely linked to tumor progression and patient outcomes. This study aimed to investigate the effects of matrix stiffness and to identify m...
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| Format: | Article |
| Language: | English |
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Korean Society of Otorhinolaryngology-Head and Neck Surgery
2025-05-01
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| Series: | Clinical and Experimental Otorhinolaryngology |
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| Online Access: | http://e-ceo.org/upload/pdf/ceo-2024-00315.pdf |
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| author | Songqun Hu Yuanru Liu Min Cheng Min Xu Huiting Liu Ying Shan Haosheng Ni Tian Xia Qicheng Zhang Zhenxin Zhang Bo You |
| author_facet | Songqun Hu Yuanru Liu Min Cheng Min Xu Huiting Liu Ying Shan Haosheng Ni Tian Xia Qicheng Zhang Zhenxin Zhang Bo You |
| author_sort | Songqun Hu |
| collection | DOAJ |
| description | Objectives Hypopharyngeal cancer (HPC), originating from the hypopharyngeal mucosa, is associated with a poor prognosis. Extracellular matrix (ECM) stiffness is closely linked to tumor progression and patient outcomes. This study aimed to investigate the effects of matrix stiffness and to identify molecular markers relevant to HPC prognosis, with the goal of improving clinical outcomes. Methods Immunohistochemical analysis and cervical enhanced computed tomography (CT) data were used to evaluate correlations among CT values, matrix stiffness, and prognosis, and to develop a prognostic model for HPC. Cell culture models with varying matrix stiffness were established using polypropylene hydrogel. Western blotting, colony formation, EDU incorporation, and Transwell assays were employed to assess the effects of matrix stiffness on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). High-throughput sequencing identified differentially expressed genes in HPC cells cultured on matrices of differing stiffness. Gene editing, in vivo subcutaneous tumorigenesis studies, and Western blotting were performed to elucidate the molecular mechanisms by which high matrix stiffness influences HPC progression and the role of ephrin A2 (EFNA2) in proliferation, migration, and EMT. Results Arterial phase CT values were positively correlated with matrix stiffness. Increased matrix stiffness was associated with lymph node metastasis, diminished therapeutic response, and poorer prognosis. Furthermore, metastatic lymph nodes in HPC patients exhibited higher CT values than those in patients with nasopharyngeal carcinoma. A high-stiffness ECM promoted proliferation, migration, and EMT in HPC cells. Mechanistically, a stiff ECM enhanced EFNA2 expression, thereby promoting proliferation, migration, EMT, and tumor growth in vivo. Conclusion EFNA2 and elevated matrix stiffness jointly contribute to the malignant phenotype in HPC. EFNA2 may represent a potential therapeutic target for managing HPC progression induced by high matrix stiffness. |
| format | Article |
| id | doaj-art-3f6345afac0f4418949b9f5ec753fd32 |
| institution | OA Journals |
| issn | 1976-8710 2005-0720 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Korean Society of Otorhinolaryngology-Head and Neck Surgery |
| record_format | Article |
| series | Clinical and Experimental Otorhinolaryngology |
| spelling | doaj-art-3f6345afac0f4418949b9f5ec753fd322025-08-20T02:03:20ZengKorean Society of Otorhinolaryngology-Head and Neck SurgeryClinical and Experimental Otorhinolaryngology1976-87102005-07202025-05-0118218819910.21053/ceo.2024.00315940EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer ProgressionSongqun Hu0Yuanru Liu1Min Cheng2Min Xu3Huiting Liu4Ying Shan5Haosheng Ni6Tian Xia7Qicheng Zhang8Zhenxin Zhang9Bo You10 Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Nantong Health College of Jiangsu Province, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, China Department of Otorhinolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, ChinaObjectives Hypopharyngeal cancer (HPC), originating from the hypopharyngeal mucosa, is associated with a poor prognosis. Extracellular matrix (ECM) stiffness is closely linked to tumor progression and patient outcomes. This study aimed to investigate the effects of matrix stiffness and to identify molecular markers relevant to HPC prognosis, with the goal of improving clinical outcomes. Methods Immunohistochemical analysis and cervical enhanced computed tomography (CT) data were used to evaluate correlations among CT values, matrix stiffness, and prognosis, and to develop a prognostic model for HPC. Cell culture models with varying matrix stiffness were established using polypropylene hydrogel. Western blotting, colony formation, EDU incorporation, and Transwell assays were employed to assess the effects of matrix stiffness on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). High-throughput sequencing identified differentially expressed genes in HPC cells cultured on matrices of differing stiffness. Gene editing, in vivo subcutaneous tumorigenesis studies, and Western blotting were performed to elucidate the molecular mechanisms by which high matrix stiffness influences HPC progression and the role of ephrin A2 (EFNA2) in proliferation, migration, and EMT. Results Arterial phase CT values were positively correlated with matrix stiffness. Increased matrix stiffness was associated with lymph node metastasis, diminished therapeutic response, and poorer prognosis. Furthermore, metastatic lymph nodes in HPC patients exhibited higher CT values than those in patients with nasopharyngeal carcinoma. A high-stiffness ECM promoted proliferation, migration, and EMT in HPC cells. Mechanistically, a stiff ECM enhanced EFNA2 expression, thereby promoting proliferation, migration, EMT, and tumor growth in vivo. Conclusion EFNA2 and elevated matrix stiffness jointly contribute to the malignant phenotype in HPC. EFNA2 may represent a potential therapeutic target for managing HPC progression induced by high matrix stiffness.http://e-ceo.org/upload/pdf/ceo-2024-00315.pdfhypopharyngeal carcinomamatrix stiffnessefna2epithelial-mesenchymal transition |
| spellingShingle | Songqun Hu Yuanru Liu Min Cheng Min Xu Huiting Liu Ying Shan Haosheng Ni Tian Xia Qicheng Zhang Zhenxin Zhang Bo You EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression Clinical and Experimental Otorhinolaryngology hypopharyngeal carcinoma matrix stiffness efna2 epithelial-mesenchymal transition |
| title | EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression |
| title_full | EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression |
| title_fullStr | EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression |
| title_full_unstemmed | EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression |
| title_short | EFNA2 Mediates Stiffness-Regulated Hypopharyngeal Cancer Progression |
| title_sort | efna2 mediates stiffness regulated hypopharyngeal cancer progression |
| topic | hypopharyngeal carcinoma matrix stiffness efna2 epithelial-mesenchymal transition |
| url | http://e-ceo.org/upload/pdf/ceo-2024-00315.pdf |
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