Sadae Hitosugi

Abstract Despite studies linking metabolism and cancer, our understanding of the metabolite network that drives metastasis remains incomplete. Through a metabolic RNAi-based screen for cell invasion, we identify alpha-aminoadipate (2-AAA), the intermediate metabolite of aminoadipic semialdehyde synthase (AASS) in the saccharopine pathway, as a common pivotal factor in metastasis of human cancers.

How mitochondrial metabolism is altered by oncogenic tyrosine kinases to promote tumor growth is incompletely understood. Here, we show that oncogenic HER2 tyrosine kinase signaling induces phosphorylation of mitochondrial creatine kinase 1 (MtCK1) on tyrosine 153 (Y153) in an ABL-dependent manner in breast cancer cells. Y153 phosphorylation, which is commonly upregulated in HER2 + breast cancers, stabilizes MtCK1 to increase the phosphocreatine energy shuttle and promote proliferation.

CPT1A Is a Regulator of Lysine Succinylation In Vivo and Can Lysine-Succinylate Enolase 1 to Inhibit Enolase 1 Activity In Vitro Because CPT1A H473A lacks both LSTase and CPTase activities (Figures 3Figures 3B and S3x Download (4.53 MB ) Document S1. Supplemental Experimental Procedures and Figures S1–S4S3G), we sought a CPT1A mutation that separates LSTase and CPTase activities so that we could assess the impact of selectively disabling the LSTase activity in cells.