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This study identifies key metabolic enzymes that protect gastric cancer cells from oxidative stress, focusing on MTHFD2. ROS levels were measured with DCFH-DA probes, and mechanistic cell and xenograft/PDX models were used to assess in vivo roles and therapeutic potential.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mthfd2-mediated-redox-homeostasis-promotes-gastric-cancer-progression-under-hypoxic-conditions-abstract-and-key-findings/330610/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mthfd2-mediated-redox-homeostasis-promotes-gastric-cancer-progression-under-hypoxic-conditions-abstract-and-key-findings/330610.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the study address about gastric cancer cells?","Question",{"text":112,"@type":113},"It addresses how gastric cancer cells survive stress driven by aberrant reactive oxygen species (ROS) production and why oxidative-stress adaptation is not fully understood.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was ROS level detected in the experiments?",{"text":117,"@type":113},"ROS levels were detected using DCFH-DA probes.",{"name":119,"@type":110,"acceptedAnswer":120},"What is the role of MTHFD2 in gastric cancer progression under hypoxia?",{"text":121,"@type":113},"Overexpression of MTHFD2 is linked with reduced overall and disease-free survival, and MTHFD2 knockdown increases ROS and induces cell death under hypoxic conditions, while inhibition reduces tumor burden in models.","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},330610,1790955536,{"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},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","REDOX REPORT  \n2024, VOL. 29, NO. 1, 2345455 [https://doi.org/10.1080/13510002.2024.2345455](https://doi.org/10.1080/13510002.2024.2345455)  \nMTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions  \nHai-Yu Mo 1,2*, Ruo-Bing Wang1*, Meng-Yao Ma 1*, Yi Zhang3, Xin-Yu Li 1, Wang-Rong Wen2, Yi Han3 and Tian Tian1 1Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, People’s Republic of China; 2Clinical Laboratory, The Affiliated Shunde Hospital of Jinan University, Foshan, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University, Guangzhou, People’s Republic of China  \nABSTRACT  \nObjectives: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the  \nkey metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress.   \nMethods: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient- derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo.   \nResults: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models.  Discussion: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2 .   \nKEYWORDS  \nGastric cancer; methylene tetrahydrofolate dehydrogenase 2 (MTHFD2); redox metabolism; NADPH; reactive oxygen species (ROS)  \n1. Introduction  \nGastric carcinogenesis (GC) remains a leading cause of cancerrelated death worldwide. Greater than one million new cases of GC were diagnosed in 2020. GC ranks fifth in incidence and fourth in mortality among cancers globally [1]. Mounting evidence suggests that many types of cancer cells, including  \nGC cells, exhibit increased levels of reactive oxygen species (ROS) compared with their normal counterparts [2–5]. Therefore, sustaining ROS homeostasis is critical for cancer cell growth and survival. Cancer cells maintain ROS homeostasis by counteracting ROS accumulation with ROS elimination through ROS-scavenging systems, which largely depend on the production of NADPH [6, 7]. Several metabolic pathways  \nCONTACT Tian Tian  [tiantian7901@yeah.net](tiantian7901@yeah.net)  No. 601 Huangpu West Avenue, Tianhe, Guangzhou, Guangdong, People’s Republic of China; Yi Han  [hany9@mail2.sysu.edu.cn](hany9@mail2.sysu.edu.cn)  No. 651 East Dongfeng Road, Guangzhou, Guangdong, People’s Republic of China; Wang-Rong Wen, No. 50, East Guizhou Avenue, Ronggui Street, Shunde District, Foshan, Guangdong, People’s Republic of China  \n*These authors contributed equally to this work.  \n Supplemental data for this article can be accessed online at [https://doi.org/10.1080/13510002.2024.2345455](https://doi.org/10.1080/13510002.2024.2345455) .  \n© 2024 The Author(s) . Published by Informa UK Limited, trading as Taylor & Francis Group  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)), which permits unrestricted use, distribution, a","cbCaioGkVNj6TpFT","https://ap.wps.com/l/cbCaioGkVNj6TpFT","pdf",2177948,11,"English","# Abstract\n## Objectives\n## Methods\n## Results\n## Discussion\n# Keywords\n# 1. Introduction","[{\"question\":\"What problem does the study address about gastric cancer cells?\",\"answer\":\"It addresses how gastric cancer cells survive stress driven by aberrant reactive oxygen species (ROS) production and why oxidative-stress adaptation is not fully understood.\"},{\"question\":\"How was ROS level detected in the experiments?\",\"answer\":\"ROS levels were detected using DCFH-DA probes.\"},{\"question\":\"What is the role of MTHFD2 in gastric cancer progression under hypoxia?\",\"answer\":\"Overexpression of MTHFD2 is linked with reduced overall and disease-free survival, and MTHFD2 knockdown increases ROS and induces cell death under hypoxic conditions, while inhibition reduces tumor burden in models.\"}]","MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions - Abstract and key findings | PDF",1789989524,28]