Publication: In vivo library screening identifies the metabolic enzyme aldolase a as a promoter of metastatic lung colonization
Program
KU-Authors
KU Authors
Co-Authors
Tu, Zhenbo
Hou, Shengqi
Zheng, Yurong
Abuduli, Maerjianghan
Intlekofer, Andrew M.
Karnoub, Antoine E
Advisor
Publication Date
2021
Language
English
Type
Journal Article
Journal Title
Journal ISSN
Volume Title
Abstract
Elucidations of the factors that promote the growth of disseminated tumor cells (DTCs) into life-threatening lesions stand to provide much needed prognostic and therapeutic targets of translational utility for patients with metastatic cancer. To identify such regulators, we conducted gain-of-function cDNA library screening to discover genes that foster prostate cancer cell colonization of mouse lungs as an experimental model. Our efforts identified the metabolic enzyme aldolase A (ALDOA) as a driver of cancer cell motility, anchorage-independent growth, and metastatic colonization, and as a prognosticator of adverse patient outcome across many malignancies, including prostate, breast, pancreatic, and liver cancers. Metabolomics coupled with biochemical and functional analyses revealed that ALDOA triggered the activation of adenosine-5'-monophosphate (AMP)activated protein kinase (AMPK), which we demonstrate played essential promalignant activities in ALDOA-expressing cells. Collectively, these findings unveiled vivo approaches to identify metastatic colonization regulators and uncovered previously undescribed roles for ALDOA-AMPK pathway in tumor progression.
Description
Source:
iScience
Publisher:
Cell Press
Keywords:
Subject
Natural science disciplines