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Editorial
. 2024 Dec;31(12):1579-1581.
doi: 10.1038/s41418-024-01400-8. Epub 2024 Oct 8.

A novel glucose sensor fuelling cancer growth

Luisa Ricci  1 , Simone Cardaci  2
Affiliations
Editorial

A novel glucose sensor fuelling cancer growth

Luisa Ricci et al. Cell Death Differ. 2024 Dec.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Glucose-mediated stabilization of HKDC1 orchestrates an oncogenic programme in cancer cells.
When glucose is available, it binds HKDC1 and masks Lys620, which hinders its ubiquitination and subsequent enzyme degradation by the proteasome. This stabilization allows HKDC1 to interact with and sequester PHB2, thereby impairing the PHB2’s inhibitory effect on the transcription factor Sp1. As a consequence, Sp1 is able to promote the expression of pro-tumour genes, enabling cancer cells proliferation. In contrast, glucose depletion promotes the exposure of Lys620 for ubiquitination and subsequent proteasome-mediated degradation of HKDC1. This results in decreased glycolysis and a concomitant increased in fatty acid oxidation. Ser896 maintains the structural conformation of the glucose binding site, which allows accessibility and ubiquitination of Lys620. As a consequence of HKDC1 degradation, PHB2 is free to translocate to the nucleus, where it inhibits Sp1-mediated expression of pro-tumour genes, ultimately slowing tumour growth. Figure created with BioRender.
See this image and copyright information in PMC

References

    1. Chen T, Xu ZG, Luo J, Manne RK, Wang Z, Hsu CC, et al. NSUN2 is a glucose sensor suppressing cGAS/STING to maintain tumorigenesis and immunotherapy resistance. Cell Metab. 2023;35:1782.e8. 10.1016/j.cmet.2023.07.009 - DOI - PMC - PubMed
    1. Miao W, Porter DF, Lopez-Pajares V, Siprashvili Z, Meyers RM, Bai Y, et al. Glucose dissociates DDX21 dimers to regulate mRNA splicing and tissue differentiation. Cell. 2023;186:80–97.e26. 10.1016/j.cell.2022.12.004 - DOI - PMC - PubMed
    1. Liu P, Luo Y, Wu H, Han Y, Wang S, Liu R, et al. HKDC1 functions as a glucose sensor and promotes metabolic adaptation and cancer growth via interaction with PHB2. Cell Death Differ. 2024. 10.1038/s41418-024-01392-5 - PMC - PubMed
    1. Irwin DM, Tan H. Molecular evolution of the vertebrate hexokinase gene family: identification of a conserved fifth vertebrate hexokinase gene. Comp Biochem Physiol - Part D Genomics Proteom. 2008;3:96–107. 10.1016/j.cbd.2007.11.002 - DOI - PubMed
    1. Zhang Y, Wang M, Ye L, Shen S, Zhang Y, Qian X, et al. HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression. Nat Commun. 2024;15:1314. 10.1038/s41467-024-45712-2 - DOI - PMC - PubMed

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