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However, these mutations are not seen in cancers, and the biological role of G\u03b113 in prostate cancer tumorigenesis is largely unexplored. Here, we report that G\u03b113 promotes anchorage-independent colony formation, spheroid formation, and xenograft tumor growth in human prostate cancer cell lines. Transcriptome analyses suggest that G\u03b113 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, G\u03b113 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 G\u03b113 loss on suppression of anchorage-independent growth. Likewise, stable knockdown of SOD2 decreased anchorage-independent cell growth, which was enhanced by overexpression of G\u03b113. These results outline a novel biological function of G\u03b113 mediated via SOD2 in prostate cancer tumorigenesis and highlight it as a potential treatment target.<\/jats:p>","DOI":"10.3390\/ijms26104883","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T04:48:18Z","timestamp":1747716498000},"page":"4883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["G\u03b113 Promotes Clonogenic Growth by Increasing Tolerance to Oxidative Metabolic Stress in Prostate Cancer Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1567-1977","authenticated-orcid":false,"given":"Di","family":"Wu","sequence":"first","affiliation":[{"name":"Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei Kiang","family":"Lim","sequence":"additional","affiliation":[{"name":"Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoran","family":"Chai","sequence":"additional","affiliation":[{"name":"Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veerabrahma Pratap","family":"Seshachalam","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"Program in Clinical and Translational Liver Cancer Research, Division of Medical Science, National Cancer Center Singapore, 30 Hospital Boulevard, Singapore 168583, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7674-7560","authenticated-orcid":false,"given":"Suhail Ahmed Kabeer","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujoy","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"Laboratory of Functional Genomics, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"Casey","sequence":"additional","affiliation":[{"name":"Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore"},{"name":"Department of Pharmacology and Cancer Biology, Duke University Medical Center, 308 Research Drive, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41388-021-02069-w","article-title":"The emerging roles of G\u03b112\/13 proteins on the hallmarks of cancer in solid tumors","volume":"41","author":"Rasheed","year":"2022","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.tips.2008.08.002","article-title":"G(12)\/G(13)-mediated signalling in mammalian physiology and disease","volume":"29","author":"Worzfeld","year":"2008","journal-title":"Trends Pharmacol. 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