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Comment
. 2022 Nov 2;41(21):e112415.
doi: 10.15252/embj.2022112415. Epub 2022 Oct 12.

Making liver cancer cells go ARGh!

Alessa L Henneberg  1   2 , Christiane A Opitz  1   3
Affiliations
Comment

Making liver cancer cells go ARGh!

Alessa L Henneberg et al. EMBO J. .

Abstract

A recent study by Missiaen et al (2022) uncovers hepatocellular carcinoma (HCC) cells to downregulate urea cycle enzymes and rely on the uptake of exogenous arginine and GCN2 kinase-dependent cell-cycle arrest for survival. These results offer new avenues for combinatorial targeting of liver cancer.

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Figures

Figure 1
Figure 1. Arginine deprivation sensitizes HCC cells to combined GCN2 inhibition and senotherapy
Urea cycle‐deficient hepatocellular carcinoma (HCC) cells depend on exogenous arginine (Arg). Upon Arg starvation, uncharged tRNA activates the GCN2‐eIF2α axis and leads to cell‐cycle arrest and increased autophagy, as well as to an increased expression of the Arg transporter SLC7A1. Additional inhibition of GCN2 disrupts this rescue mechanism but increases the number of senescent cells. Arg deprivation and GCN2 inhibition, combined with senotherapy, lead to apoptosis in HCC cells.
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References

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