Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells

• DOI: 10.1038/s41417-021-00326-4
• Publication Date: 2021-04-08T08:03:25Z
• Authors: Tatsunori Suzuki; Takahiro Kishikawa; Tatsuyuki Sato; Norihiko Takeda; Yuki Sugiura; Takahiro Seimiya; Kazuma Sekiba; Motoko Ohno; Takuma Iwata; Rei Ishibashi; Motoyuki Otsuka; Kazuhiko Koike
• Keywords: Reprogramming

Abstract Mutational activation of the KRAS gene occurs in almost all pancreatic ductal adenocarcinoma (PDAC) and is earliest molecular event their carcinogenesis. Evidence has accumulated metabolic reprogramming PDAC, such as amino acid homeostasis autophagic flux. However, biological effects mutation on at earlier stages PDAC carcinogenesis are unclear. Here we report dynamic immortalized human non-cancerous epithelial cells, which a was induced by gene-editing, may mimic early Similar to cases increased dependency glucose glutamine for maintaining intracellular redox balance. In addition, levels acids were significantly decreased because active protein synthesis, cells required greater flux maintain viability. The lysosomal inhibitor chloroquine inhibited cell proliferation. Therefore, an initiated mutation, suggesting rationale development nutritional interventions that suppress or delay PDAC.