Lactate jump‐starts mTORC 1 in cancer cells

Abstract

The kinase mammalian target of rapamycin (mTOR) is a major regulatory hub that senses and integrates nutrient, energy, and growth factor inputs to promote cell growth. In this issue of EMBO Reports, Byun et al [1] report that high intracellular levels of lactate activate mTORC1 in KRAS transformed cells independently of a growth factor input. This suggests a mechanism for how mTORC1 can be co‐opted to support oncogenic growth and proliferation.See also: JK Byun et al (June 2019)EMBO Reports (2019) 20: e48302OpenUrlAbstract/FREE Full TextLactate production is increased in many tumors as a consequence of the Warburg effect, where cancer cells generate ATP preferentially via glycolysis despite the availability of oxygen. Lactate is the metabolic end product of glycolysis and is often dismissed as an unwanted by‐product that is discarded from the cell. However, recent studies have revealed an active role for lactate in cancer metabolism. There are several scenarios where tumor cells utilize lactate as a carbon source. For example, in the case of metabolic symbiosis, lactate generated in the inner, hypoxic core of a tumor is utilized by cells in the periphery of the tumor where oxygen levels are sufficient to support the back …