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This study examined how lipid-metabolism-driven ferroptosis contributes to drug resistance and DTP generation in HNSCC. High FSP1 expression was linked to relapse after cisplatin, supported by RNA sequencing and patient-derived DTP models. 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Their persister state is associated with temporary molecular reprogramming that enables treatment evasion.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What did the study identify regarding FSP1 and lipid metabolism?",{"text":117,"@type":113},"Relapse tissues after cisplatin showed higher FSP1 levels and increased expression of lipid-metabolism-related genes. This pattern was consistent in primary DTP cells and supported by the Cancer Genome Atlas.",{"name":119,"@type":110,"acceptedAnswer":120},"How does targeting FSP1 relate to ferroptosis and chemoresistance?",{"text":121,"@type":113},"The findings connect FSP1-driven regulation of intracellular iron homeostasis and lipid metabolism to ferroptosis pathways involved in DTP generation and acquired chemoresistance. In vivo testing used ferroptosis induction to evaluate anti-tumor effects.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331813,1790988281,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","[www.aging-us.com](www.aging-us.com) AGING 2024, Vol. 16, No. 1  \nResearch Paper  \nTargeting of FSP1 regulates iron homeostasis in drug-tolerant persister head and neck cancer cells via lipid-metabolism-driven ferroptosis  \nYang-Che Wu1,2, Chin-Sheng Huang1,2, Ming-Shou Hsieh1,2, Chih-Ming Huang3,4, Syahru Agung Setiawan5,6, Chi-Tai Yeh5,6,7, Kuang-Tai Kuo8,9, Shao-Cheng Liu10  \n1 Department of Dentistry, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan 2School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei City 11031, Taiwan 3 Department of Otolaryngology, Taitung Mackay Memorial Hospital, Taitung City 950408, Taiwan 4 Department of Nursing, Tajen University, Yanpu 90741, Pingtung County, Taiwan  \n5 International Ph. D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan  \n6 Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan  \n7Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung City 95092, Taiwan  \n8 Division of Thoracic Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 11031, Taiwan  \n9 Division of Thoracic Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan  \n10 Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan  \nCorrespondence to: Ming-Shou Hsieh, Shao-Cheng Liu; email: [22057@s.tmu.edu.tw](22057@s.tmu.edu.tw), [m871435@mail.ndmctsgh.edu.tw](m871435@mail.ndmctsgh.edu.tw)[ ](m871435@mail.ndmctsgh.edu.tw)[Keywords:](Keywords: drug-tolerant persister cancer cells)[ drug-tolerant persister cancer cells](Keywords: drug-tolerant persister cancer cells), [tumor organoids](tumor organoids), [ferroptosis](ferroptosis), FSP1  \nReceived: May 17, 2023 Accepted: November 15, 2023 Published: January 10, 2024  \nCopyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.  \nABSTRACT  \nBackground: Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. The persister state in cancer cells arises due to temporary molecular reprogramming, and exploring the genetic composition and microenvironment during the development of head and neck squamous cell carcinoma (HNSCC) can enhance our comprehension of the types of cell death that HNSCC, thus identifying potential targets for innovative therapies. This project investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in HNSCC. Methods: High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated.  \nResults: We generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets in vitro. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. We ","cbCaiq9v8lTdplK6","https://ap.wps.com/l/cbCaiq9v8lTdplK6","pdf",1542730,21,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions","[{\"question\":\"What role do drug-tolerant persister (DTP) cells play in HNSCC recurrence?\",\"answer\":\"DTP cells provide a reservoir that supports disease recurrence. Their persister state is associated with temporary molecular reprogramming that enables treatment evasion.\"},{\"question\":\"What did the study identify regarding FSP1 and lipid metabolism?\",\"answer\":\"Relapse tissues after cisplatin showed higher FSP1 levels and increased expression of lipid-metabolism-related genes. This pattern was consistent in primary DTP cells and supported by the Cancer Genome Atlas.\"},{\"question\":\"How does targeting FSP1 relate to ferroptosis and chemoresistance?\",\"answer\":\"The findings connect FSP1-driven regulation of intracellular iron homeostasis and lipid metabolism to ferroptosis pathways involved in DTP generation and acquired chemoresistance. In vivo testing used ferroptosis induction to evaluate anti-tumor effects.\"}]","Targeting of FSP1 regulates iron homeostasis in drug-tolerant persister head and neck cancer cells via lipid-metabolism-driven ferroptosis | PDF",1789995286,53]