Abstract
Pancreatic cancer is associated with high mortality, and pancreatic ductal adenocarcinoma (PDAC) is its most common subtype. The rapid growth of PDAC is dependent on the non-canonical pathway of glutamine (Gln) utilization, and loss of heterozygosity for KrasG12D (KrasG12D-LOH) frequently observed in PDAC is associated with an aggressive and invasive phenotype. However, it remains unclear whether KrasG12D-LOH contributes to non-canonical Gln metabolism in PDAC. Here, we showed that KrasG12D-LOH leads to a substantial increase in non-canonical Gln metabolism in PDAC cells. Importantly, we observed elevated expression of regulated in DNA damage and development 1 (REDD1), which is activated in response to hypoxia and nutrient deprivation, in KrasG12D-LOH PDAC, and that REDD1 knockdown efficiently repressed KrasG12D-LOH-regulated Gln metabolism and suppressed proliferation, migration, and invasion of KrasG12D-LOH PDAC cells. These data provide evidence that REDD1 is a downstream target of KrasG12D-LOH and is involved in promoting non-canonical Gln metabolism in PDAC.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Biochemical and Biophysical Research Communications
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
