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While PKM2 is widely regarded as a tumor-promoting factor in many cancers, its regulatory role in head and neck carcinogenesis required clarification. PKM2 mRNA and protein were assessed in head and neck tumor specimens, and shRNA-mediated PKM2-deficient HNSC cells were used to define its function. PKM2 expression was enriched in HNSC tissues, yet inversely associated with tumor stage and linked to higher recurrence-free survival, suggesting tumor-suppressive activity through metabolic reprogramming.",{"@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/pyruvate-kinase-differentially-alters-metabolic-signatures-during-head-and-neck-carcinogenesis/380710/",{"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/pyruvate-kinase-differentially-alters-metabolic-signatures-during-head-and-neck-carcinogenesis/380710.png","ImageObject",300,407,{"name":92,"@type":93},"Well Done","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does PKM2 play during glycolysis in this study?","Question",{"text":112,"@type":113},"PKM2 produces ATP during glycolysis by catalyzing the dephosphorylation of PEP into pyruvate, linking PKM2 activity to cellular energy production.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is PKM2 expression related to tumor stage and patient outcomes?",{"text":117,"@type":113},"PKM2 mRNA expression reversely correlates with tumor stage, and the PKM2high HNSC population shows greater recurrence-free survival, indicating a possible tumor-suppressive role.",{"name":119,"@type":110,"acceptedAnswer":120},"What phenotypic and molecular changes occur when PKM2 is lost in HNSC cells?",{"text":121,"@type":113},"PKM2 loss increases in vivo xenograft tumor growth and enhances cisplatin resistance, while reducing cell motility; molecularly, it shifts metabolism toward mitochondrial metabolism and activates PKB/Akt and ERK signaling.","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},380710,1790624149,{"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":14,"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":36},5909892210082,"https://ap-avatar.wpscdn.com/avatar/56001069da27c9f41e8?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789614185077863061","Article  \nPyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis  \nPei-Chun Huang 1, Ching-Wen Chang 2,3, Yu-Cheng Lin 4,5, Chang-Yi Chen 1, Tsai-Ying Chen 1, Lu-Te Chuang 6, Chung-Ji Liu 4,7,8, Chien-Ling Huang 9 and Wan-Chun Li 1,4,5, *  \nCitation: Huang, P.-C.; Chang, C.-W.; Lin, Y.-C.; Chen, C.-Y.; Chen, T.-Y.; Chuang, L.-T.; Liu, C.-J.; Huang, C.-L.; Li, W.-C. Pyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis. Int. J. Mol. Sci. 2023, 24, 16639. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms242316639  \nAcademic Editor: Alfred King-Yin Lam  \nReceived: 16 October 2023  \nRevised: 13 November 2023  \nAccepted: 16 November 2023  \nPublished: 23 November 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; [peijyng@gmail.com](peijyng@gmail.com) (P.-C.H.); [cychen.de10@nycu.edu.tw](cychen.de10@nycu.edu.tw) (C.-Y.C.); [puddy0906@gmail.com](puddy0906@gmail.com) (T.-Y.C.)  \n2 Graduate Institute of Metabolism and Obesity Sciences (GIMOS), College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; [changc11@tmu.edu.tw](changc11@tmu.edu.tw)  \n3 Taipei Cancer Center, Taipei Medical University, Taipei 11031, Taiwan  \n4 Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; [ylin@nycu.edu.tw](ylin@nycu.edu.tw) (Y.-C.L.); [cjliu3229@gmail.com](cjliu3229@gmail.com) (C.-J.L.)  \n5 Oral Medicine Innovation Center (OMIC), National Yang Ming Chiao Tung University, Taipei 11221, Taiwan  \n6 Department of Biotechnology and Pharmaceutical Technology, Yuanpei University of Medical Technology, Hsinchu 30015, Taiwan; [ltchuang@mail.ypu.edu.tw](ltchuang@mail.ypu.edu.tw)  \n7 Department of Oral and Maxillofacial Surgery, MacKay Memorial Hospital, Taipei 10449, Taiwan  \n8 Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan  \n9 Department of Health Technology and Informatics (HTI), The Hong Kong Polytechnic University (PolyU), Hung Hom, Kowloon, Hong Kong SAR, China; [cl.huang@polyu.edu.hk](cl.huang@polyu.edu.hk)  \n* [Correspondence: wcli@nycu.edu.tw](Correspondence: wcli@nycu.edu.tw); Tel.: +886-2-28267255; Fax: +886-2-28264053  \nAbstract: During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered asa tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expression was examined in head and neck tumorous specimens. The role of PKM2 in controlling cellular malignancy was determined in shRNA-mediated PKM2-deficient head and neck squamous cell carcinoma (HNSC) cells. In agreement with the results in other cancers, PKM2 expression is enriched in both mouse and human HNSC tissues. Nevertheless, PKM2 mRNA expression reversely correlated with tumor stage, and greater recurrence-free survival rates are evident in the PKM2high HNSC population, arguing that PKM2 may be tumor-suppressive. Multifaceted analyses showed a greater in vivo xenografic tumor growth and an enhanced cisplatin resistance in response to PKM2 loss, whereas PKM2 silencing led to reduced cell motility. At the molecular level, metabolic shifts towards mitochondrial metabolism and activation of oncogenic Protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK) signals were detected in PKM2-silencing HNSC cells. In sum, our finding","cbCaif6OhZw4smBE","https://ap.wps.com/l/cbCaif6OhZw4smBE","pdf",3809660,16,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What role does PKM2 play during glycolysis in this study?\",\"answer\":\"PKM2 produces ATP during glycolysis by catalyzing the dephosphorylation of PEP into pyruvate, linking PKM2 activity to cellular energy production.\"},{\"question\":\"How is PKM2 expression related to tumor stage and patient outcomes?\",\"answer\":\"PKM2 mRNA expression reversely correlates with tumor stage, and the PKM2high HNSC population shows greater recurrence-free survival, indicating a possible tumor-suppressive role.\"},{\"question\":\"What phenotypic and molecular changes occur when PKM2 is lost in HNSC cells?\",\"answer\":\"PKM2 loss increases in vivo xenograft tumor growth and enhances cisplatin resistance, while reducing cell motility; molecularly, it shifts metabolism toward mitochondrial metabolism and activates PKB/Akt and ERK signaling.\"}]","Pyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis | PDF",1790241403]