biostudies-literatureNimmakayala RKDH | NIHR | Health Services Research ProgrammeNCI NIH HHS215-231https://www.ebi.ac.uk/biostudies/studies/S-EPMC10041665biostudies-literatureUnknown40(1)Pancreatic ductal adenocarcinoma (PDAC) metastasizes to distant organs, which is the primary cause of mortality; however, specific features mediating organ-specific metastasis remain unexplored. Emerging evidence demonstrates that cancer stem cells (CSCs) and cellular metabolism play a pivotal role in metastasis. Here we investigated the role of distinct subtypes of pancreatic CSCs and their metabolomic signatures in organ-specific metastatic colonization. We found that PDAC consists of ALDH+/CD133+ and drug-resistant (MDR1+) subtypes of CSCs with specific metabolic and stemness signatures. Human PDAC tissues with gemcitabine treatment, autochthonous mouse tumors from Kras^G12D; Pdx1-Cre (KC) and Kras^G12D; Trp53^R172H; Pdx-1 Cre (KPC) mice, and KPC- Liver/LunOncogeneMetabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma.PMC10041665R01 CA210637U01 CA200466R01 CA195586R01 CA183459R01 CA247471R01 CA201444U01 CA210240P01 CA217798R01 CA228524Gupta RRauth SShailendra GKChirravuri RGrandgenett PMChhonker YSPonnusamy MPRachagani SNimmakayala RKMallya KLeon FL Grem JMurry DJMarimuthu SHollingsworth MAPrajapati DRLele SMC Caffrey TBatra SKNallasamy PChugh SfalseMetabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma.Pancreatic ductal adenocarcinoma (PDAC) metastasizes to distant organs, which is the primary cause of mortality; however, specific features mediating organ-specific metastasis remain unexplored. Emerging evidence demonstrates that cancer stem cells (CSCs) and cellular metabolism play a pivotal role in metastasis. Here we investigated the role of distinct subtypes of pancreatic CSCs and their metabolomic signatures in organ-specific metastatic colonization. We found that PDAC consists of ALDH+/CD133+ and drug-resistant (MDR1+) subtypes of CSCs with specific metabolic and stemness signatures. Human PDAC tissues with gemcitabine treatment, autochthonous mouse tumors from Kras^G12D; Pdx1-Cre (KC) and Kras^G12D; Trp53^R172H; Pdx-1 Cre (KPC) mice, and KPC- Liver/Lun2021-01-01T00:00:00Z2021 Jan2025-04-04T20:20:36.259Z2025-04-04T20:20:36.259ZS-EPMC100416653311023510.1038/s41388-020-01518-2