Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence

摘要: Summary Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player breast cancer metastasis. ACC1 phosphorylation was increased invading cells both murine human cancer, serving point convergence for leptin transforming growth factor (TGF) β signaling. mediated by TGFβ-activated kinase (TAK) 1, inhibition indispensable elevation cellular acetyl-CoA, subsequent increase Smad2 transcription acetylation activation, ultimately epithelial-mesenchymal transition induction. deficiency worsened upon primary resection mice, levels correlated with metastatic potential lung patients. Given demonstrated effectiveness anti-leptin receptor antibody treatment halting ACC1-dependent invasiveness, our work defines "metabolocentric" approach therapy.