Autophagy is required for proper cysteine homeostasis in pancreatic cancer through regulation of SLC7A11.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is highly refractory to current therapies. We had previously shown that PDAC can utilize its high levels of basal autophagy to support its metabolism and maintain tumor growth. Consistent with the importance of autophagy in PDAC, autophagy inhibition significantly enhances response of PDAC patients to chemotherapy in two randomized clinical trials. However, the specific metabolite(s) that autophagy provides to support PDAC growth is not yet known. In this study, we demonstrate that under nutrient-replete conditions, loss of autophagy in PDAC leads to a relatively restricted impairment of amino acid pools, with cysteine levels showing a significant drop. Additionally, we made the striking discovery that auto

SUBMITTER: Mukhopadhyay S 

PROVIDER: S-EPMC8017731 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature