Unknown

Dataset Information

0

Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport.


ABSTRACT: Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK). In turn, AMPK activates FOXO3A and its transcriptional target, PUMA, which induces anoikis to suppress PDAC tumor growth and metastasis. Pharmacological or genetic activation of AMPK, similar to PON2 inhibition, blocks PDAC tumor growth. Collectively, our results identify PON2 as a new modulator of glucose transport that regulates a pharmacologically tractable pathway necessary for PDAC tumor growth and metastasis.

SUBMITTER: Nagarajan A 

PROVIDER: S-EPMC5567863 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport.

Nagarajan Arvindhan A   Dogra Shaillay Kumar SK   Sun Lisha L   Gandotra Neeru N   Ho Thuy T   Cai Guoping G   Cline Gary G   Kumar Priti P   Cowles Robert A RA   Wajapeyee Narendra N  

Molecular cell 20170810 4


Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via  ...[more]

Similar Datasets

| S-EPMC3289356 | biostudies-literature
| S-EPMC9440910 | biostudies-literature
| S-EPMC6958723 | biostudies-literature
| S-EPMC9867014 | biostudies-literature
| S-EPMC5268469 | biostudies-literature
| S-EPMC1138093 | biostudies-other
| S-EPMC7017733 | biostudies-literature
| S-EPMC7426874 | biostudies-literature
| S-EPMC8365240 | biostudies-literature
| S-EPMC9174867 | biostudies-literature