Fig 2: PDP1 induced PDAC cell proliferation and migration by inducing intracellular ATP. a PDP1 overexpression induced intracellular ATP content, while its knockdown reduced ATP levels. Supplementation of an alternative substrate of ATP production, acetate, restored cell proliferation (b), colony formation (c) and migration of PDP1 knockdown PDAC cells (d). ***p < 0.001

Fig 3: PDP1 regulated PDAC cell proliferation and migration in vitro. a Transfection of the PDP1 ORF clone or shRNA regulated endogenous expression of PDP1 in PDAC cells. b Overexpression of PDP1 promoted PDAC cell proliferation, while PDP1 suppressed PDAC cell proliferation. c Overexpression of PDP1 promoted colony formation of PDAC cells, while PDP1 suppressed PDAC cell colony number. d Overexpression of PDP1 promoted PDAC cell migration, while PDP1 suppressed PDAC cell migration. ***p < 0.001

Fig 4: AMPK inactivation was responsible for PDP1-mediated PDAC cell proliferation and migration. a PDP1 overexpression suppressed AMPK signaling, while its knockdown induced activation via phosphorylation. b The presence of compound C (20 mM) inactivated AMPK signaling in PDP1 knockdown PDAC cells, which in turn reactivated mTOR signaling. Reactivation of mTOR restored cell proliferation (c), colony formation (d), and migration of PDP1 knockdown PDAC cells (e). f AMP was supplemented in the PDP1-overexpressing cells to adjust the intracellular AMP:ATP ratio. Increased AMP:ATP ratio in the PDP-overexpressing cells resulted in the restoration of AMPK activity but mTOR repression. ***p < 0.001

Fig 5: PDP1 was overexpressed in PDAC. Data were retrieved from the GEO database, and PDP1 was found to be overexpressed in PDAC tissues compared with normal pancreatic tissues in (a) GSE15471 and (b) GSE28735. c Immunohistochemical staining of PDP1 was retrieved from the Human Protein Atlas, which suggested that PDP1 protein expression was upregulated in PDAC tissues. Survival of PDAC patients was retrieved from TGCA database, and patients with PDP1 expression above the median level had poor (d) overall survival and (e) disease-free survival. f Surviving PDAC patients had lower expression of PDP1 than the censored patients