RAC1 directly phosphorylates both PKM2 and FBP1 to promote radioresistance in hepatocellular carcinoma.
Radiotherapy (RT) is a promising treatment for hepatocellular carcinoma (HCC), but resistance limits its efficacy.
APA
Jiang Y, Zhou K, et al. (2026). RAC1 directly phosphorylates both PKM2 and FBP1 to promote radioresistance in hepatocellular carcinoma.. Molecular therapy : the journal of the American Society of Gene Therapy, 34(2), 1201-1214. https://doi.org/10.1016/j.ymthe.2025.10.049
MLA
Jiang Y, et al.. "RAC1 directly phosphorylates both PKM2 and FBP1 to promote radioresistance in hepatocellular carcinoma.." Molecular therapy : the journal of the American Society of Gene Therapy, vol. 34, no. 2, 2026, pp. 1201-1214.
PMID
41204670
Abstract
Radiotherapy (RT) is a promising treatment for hepatocellular carcinoma (HCC), but resistance limits its efficacy. This study reveals that Rac family small GTPase 1 (RAC1) is overexpressed in radioresistant HCC patients and promotes resistance by directly phosphorylating pyruvate kinase M2 (PKM2) and fructose-1,6-bisphosphatase 1 (FBP1), leading to enhanced glycolytic flux. Introducing mutations in PKM2 (S172A) and FBP1 (T309A) effectively inhibits tumor growth. Additionally, combining RT with the US Food and Drug Administration-approved drug foscarnet sodium, which inhibits RAC1 activity, significantly improves therapeutic outcomes in vivo. These findings identify RAC1 as a key regulator of radioresistance and a potential therapeutic target in HCC.
MeSH Terms
Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Animals; rac1 GTP-Binding Protein; Radiation Tolerance; Mice; Membrane Proteins; Thyroid Hormone-Binding Proteins; Thyroid Hormones; Phosphorylation; Fructose-Bisphosphatase; Cell Line, Tumor; Carrier Proteins; Xenograft Model Antitumor Assays; Gene Expression Regulation, Neoplastic
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