Therapeutic arginine starvation in ASS1-deficient cancers inhibits the Warburg effect

Mol Cell Oncol. 2017 Mar 1;4(3):e1295131. doi: 10.1080/23723556.2017.1295131. eCollection 2017.


Argininosuccinate Synthetase 1 deficiency induces dependence on extracellular arginine for continued cellular growth and survival. Arginine starvation inhibits the Warburg effect and diverts glucose into serine biosynthesis, while simultaneously increasing glutamine metabolism via the tricarboxylic acid cycle. Simultaneous arginine deprivation and inhibition of the subsequent metabolic adaptations induce synthetic lethality.

Keywords: ADI-PEG20; ASS1; GLS; PHGDH; Warburg; arginine deiminase; argininosuccinate synthetase 1; glucose; glutaminase; glutamine; metabolism.