Publication: In vivo library screening identifies the metabolic enzyme aldolase A as a promoter of metastatic lung colonization
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Tu, Zhenbo
Hou, Shengqi
Zheng, Yurong
Abuduli, Maerjianghan
Intlekofer, Andrew M.
Karnoub, Antoine E.
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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.
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Elsevier
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Science and technology
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Has Part
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iScience
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DOI
10.1016/j.isci.2021.102425