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This work shows that Gα13 enhances anchorage-independent colony formation, spheroid formation, and xenograft tumor growth in human prostate cancer cell lines. Transcriptome analyses indicate mitochondrial gene programs and oxidative stress response regulation, while GNA13 silencing elevates mitochondrial superoxide and increases sensitivity to oxidative metabolic stress. The study links these effects to SOD2 abundance and promoter activity, where SOD2 expression rescues loss of Gα13 and SOD2 knockdown suppresses anchorage-independent growth, supporting Gα13-SOD2 as a potential treatment target.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/g13-promotes-clonogenic-growth-by-increasing-tolerance-to-oxidative-metabolic-stress-in-prostate-cancer-cells/370568/",{"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/g13-promotes-clonogenic-growth-by-increasing-tolerance-to-oxidative-metabolic-stress-in-prostate-cancer-cells/370568.png","ImageObject",300,407,{"name":92,"@type":93},"Riley West","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What cellular growth behaviors does Gα13 enhance in prostate cancer cells?","Question",{"text":113,"@type":114},"Gα13 promotes anchorage-independent colony formation, spheroid formation, and xenograft tumor growth in human prostate cancer cell lines.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does Gα13 affect oxidative metabolic stress and mitochondrial reactive oxygen species?",{"text":118,"@type":114},"Silencing GNA13 increases mitochondrial superoxide levels and heightens sensitivity to oxidative metabolic stress under non-glycolytic conditions.",{"name":120,"@type":111,"acceptedAnswer":121},"What role does SOD2 play in the Gα13-driven phenotype?",{"text":122,"@type":114},"Gα13 influences mitochondrial SOD2 abundance, SOD2 promoter activity, and SOD2 mRNA expression; restoring SOD2 rescues Gα13 loss effects, while stable SOD2 knockdown suppresses anchorage-independent growth.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},370568,1790673471,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1099523885074,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Article  \nGα13 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells  \nDi Wu 1, Wei Kiang Lim 1, Xiaoran Chai 1,2, Veerabrahma Pratap Seshachalam 2,3, Suhail Ahmed Kabeer Rasheed 1, Sujoy Ghosh 2,4 and Patrick J. Casey 1,5, *  \nAcademic Editors: Domenica Mangieri and Annamaria Piscazzi  \nReceived: 9 March 2025  \nRevised: 7 May 2025  \nAccepted: 10 May 2025  \nPublished: 20 May 2025  \nCitation: Wu, D.; Lim, W.K.; Chai, X.; Seshachalam, V.P.; Rasheed, S.A.K.; Ghosh, S.; Casey, P.J. Gα13 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells. Int. J. Mol. Sci. 2025, 26, 4883. [https://](https://)[ ](https://)[doi.org/10.3390/ijms26104883](doi.org/10.3390/ijms26104883)  \n[Copyright:](Copyright:) © 2025 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://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) .  \n1 Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore  \n2 Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore  \n3 Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore  \n4 Laboratory of Functional Genomics, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA  \n5 Department of Pharmacology and Cancer Biology, Duke University Medical Center, 308 Research Drive, Durham, NC 27710, USA  \n* [Correspondence: patrick.casey@duke-nus.edu.sg](Correspondence: patrick.casey@duke-nus.edu.sg)  \nAbstract: The oncogenic role of the G12 family in many human solid cancers has been extensively studied, primarily through the effects of constitutively active mutants of these proteins on cell migration and invasion. However, these mutations are not seen in cancers, and the biological role of Gα13 in prostate cancer tumorigenesis is largely unexplored. Here, we report that Gα13 promotes anchorage-independent colony formation, spheroid formation, and xenograft tumor growth in human prostate cancer cell lines. Transcriptome analyses suggest that Gα13 modulates genes in the mitochondria and are involved in the oxidative stress response. Silencing of GNA13 increased mitochondrial superoxide levels when prostate cancer cells were cultured in galactose medium and increased the sensitivity to oxidative metabolic stress when the cells were cultured in media containing non-glycolytic metabolites. Furthermore, Gα13 levels impacts the abundance of superoxide dismutase 2 (SOD2) in the mitochondria, as well as SOD2 promoter activity and mRNA expression. Importantly, expression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent growth. Likewise, stable knockdown of SOD2 decreased anchorage-independent cell growth, which was enhanced by overexpression of Gα13 . These results outline a novel biological function of Gα13 mediated via SOD2 in prostate cancer tumorigenesis and highlight it as a potential treatment target.  \nKeywords: Gα13; GNA13; prostate cancer; superoxide; superoxide dismutase; SOD2; oxidative metabolic stress; mitochondria; LNCaP; PC3  \n1. Introduction  \nGα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors (GPCRs) . The oncogenic role ofGα13 in several human cancers has been extensively studied and can be distinct from that of Gα12 [1–3] . Analysis of patient samples indicate that Gα13 expression correlates with survival in solid cancers such as gastric [4], hepatocellular [5], esophageal [6] and head and neck [7] cancers.","cbCailc3Ht0Bujmi","https://ap.wps.com/l/cbCailc3Ht0Bujmi","pdf",3041328,18,"English","# Introduction\n## Gα13 in the G12 protein family and cancer associations\n## Oxidative stress response and Nrf2 regulation\n## SOD2 biology in prostate tumors","[{\"question\":\"What cellular growth behaviors does Gα13 enhance in prostate cancer cells?\",\"answer\":\"Gα13 promotes anchorage-independent colony formation, spheroid formation, and xenograft tumor growth in human prostate cancer cell lines.\"},{\"question\":\"How does Gα13 affect oxidative metabolic stress and mitochondrial reactive oxygen species?\",\"answer\":\"Silencing GNA13 increases mitochondrial superoxide levels and heightens sensitivity to oxidative metabolic stress under non-glycolytic conditions.\"},{\"question\":\"What role does SOD2 play in the Gα13-driven phenotype?\",\"answer\":\"Gα13 influences mitochondrial SOD2 abundance, SOD2 promoter activity, and SOD2 mRNA expression; restoring SOD2 rescues Gα13 loss effects, while stable SOD2 knockdown suppresses anchorage-independent growth.\"}]","Gα13 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells | PDF",1790189210,45]