American Association for Cancer Research
Browse
15417786mcr170061-sup-178448_2_supp_data_4046689_cq4zpr.png (342.51 kB)

Figure S2 from PPARδ Reprograms Glutamine Metabolism in Sorafenib-Resistant HCC

Download (342.51 kB)
figure
posted on 2023-04-03, 17:23 authored by Mi-Jin Kim, Yeon-Kyung Choi, Soo Young Park, Se Young Jang, Jung Yi Lee, Hye Jin Ham, Byung-Gyu Kim, Hui-Jeon Jeon, Ji-Hyun Kim, Jung-Guk Kim, In-Kyu Lee, Keun-Gyu Park

Figure S2 shows relative amount of intracellular glutamine level and abundance of indicated protein levels in sorafenib-sensitive and -resistant HCC cells.

Funding

National Research Foundation of Korea

Ministry of Science, ICT and Future Planning

History

ARTICLE ABSTRACT

The tyrosine kinase inhibitor sorafenib is the only therapeutic agent approved for the treatment of advanced hepatocellular carcinoma (HCC), but acquired resistance to sorafenib is high. Here, we report metabolic reprogramming in sorafenib-resistant HCC and identify a regulatory molecule, peroxisome proliferator–activated receptor-δ (PPARδ), as a potential therapeutic target. Sorafenib-resistant HCC cells showed markedly higher glutamine metabolism and reductive glutamine carboxylation, which was accompanied by increased glucose-derived pentose phosphate pathway and glutamine-derived lipid biosynthetic pathways and resistance to oxidative stress. These glutamine-dependent metabolic alterations were attributed to PPARδ, which was upregulated in sorafenib-resistant HCC cells and human HCC tissues. Furthermore, PPARδ contributed to increased proliferative capacity and redox homeostasis in sorafenib-resistant HCC cells. Accordingly, inhibiting PPARδ activity reversed compensatory metabolic reprogramming in sorafenib-resistant HCC cells and sensitized them to sorafenib. Therefore, targeting compensatory metabolic reprogramming of glutamine metabolism in sorafenib-resistant HCC by inhibiting PPARδ constitutes a potential therapeutic strategy for overcoming sorafenib-resistance in HCC.Implications: This study provides novel insight into the mechanism underlying sorafenib resistance and a potential therapeutic strategy targeting PPARδ in advanced hepatocellular carcinoma. Mol Cancer Res; 15(9); 1230–42. ©2017 AACR.

Usage metrics

    Molecular Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC