mTORC1 maintains metabolic balance

Abstract

Anticancer therapeutics aimed at the inhibition of mTORC1 activity shift metabolism to favor the degradation of extracellular proteins. Recently Thompson and colleagues demonstrated a novel regulatory mechanism whereby mTORC1 plays a distinct role as a key regulator of metabolism depending on the environmental nutrient status.

Figure 1

Schematic diagram illustrating the limitation of mTORC1 inhibitors for anticancer therapy. (A) Anabolic cellular metabolism involving the PI3K-mTORC1 pathway predominantly leads to cancer proliferation, while simultaneously suppressing catabolic cellular metabolism, which is required for cell growth and survival during nutrient starvation. This metabolic balance is finely controlled by mTORC1. (B) When mTORC1 is inhibited by treatment with targeted therapeutics or environmental nutrient deprivation, catabolic processes including macroautophagy and lysosome-dependent degradation of extracellular proteins derived from macropinocytosis are significantly increased to support cancer cell proliferation, ultimately affecting drug efficacy depending on the tumor microenvironment.