Stephano S. Mello

Abstract Restricting amino acids from tumours is an emerging therapeutic strategy with substantial promise1. Although typically considered an intracellular antioxidant with tumour-promoting capabilities2, glutathione (GSH), as a tripeptide of cysteine, glutamate and glycine, can be catabolized to release amino acids. The extent to which GSH-derived amino acids are essential to cancers is unclear.

Abstract The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53's critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of TP53 mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC.

Figure 2p53 Transcriptomics and ChIP-Seq Analysis Reveal Genes Hyperactivated by p5353,54(A) Genes activated in both HrasV12;Trp5353,54/53,54 and HrasV12;Trp53+/+ MEFs relative to HrasV12;Trp53?/? MEFs were further filtered based on fold change (HrasV12;Trp5353,54/53,54 versus HrasV12;Trp53+/+ ? 1.3-fold) and on direct binding by p53, as established by p53 ChIP-seq data.