GLS and cancer: For example, SIRT4 inhibits the proliferation of cancer cells by inhibiting glutamine metabolism.341,342 In addition, cell proliferation due to repression of SIRT4 by the mTORC1 pathway has been identified.343 Moreover, SIRT4 is the molecular switch mediating cellular proliferation through glutaminase (GLS)-mediated activation of the Akt/GSK3β/CyclinD1 pathway; mechanically, SIRT4 suppression activates glutaminase, thereby initiating Akt activation.344