Cancer
Cancer Systems Biology
Metabolomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
21 May 2021
21 May 2021
Historique:
received:
05
10
2020
revised:
22
02
2021
accepted:
09
04
2021
entrez:
26
5
2021
pubmed:
27
5
2021
medline:
27
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34036247
doi: 10.1016/j.isci.2021.102425
pii: S2589-0042(21)00393-X
pmc: PMC8138724
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102425Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207322
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA251543
Pays : United States
Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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