TSC2 and cancer: On the one hand, EZH2 inhibition-triggered autophagy induces cell death of cancer cells62,63 and aortic vascular smooth muscle cells,64 liver injury65 and also helps bacterial elimination.57 In cancer cells, metastasis-associated 1 family member 2 (MTA2) first recognizes unmodified H3 with its SANT domain, then recruits EZH2 to a set of mTOR pathway-related genes, such as TSC2, RHOA, and DEPTOR, which are negative regulators of the mTOR signaling pathway, resulting in increased H3K27me3 accompanied by reduced H3K27ac at the promoters.