Document Detail


Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition.
MedLine Citation:
PMID:  25171410     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
It is increasingly appreciated that oncogenic transformation alters cellular metabolism to facilitate cell proliferation, but less is known about the metabolic changes that promote cancer cell aggressiveness. Here, we analyzed metabolic gene expression in cancer cell lines and found that a set of high-grade carcinoma lines expressing mesenchymal markers share a unique 44 gene signature, designated the "mesenchymal metabolic signature" (MMS). A FACS-based shRNA screen identified several MMS genes as essential for the epithelial-mesenchymal transition (EMT), but not for cell proliferation. Dihydropyrimidine dehydrogenase (DPYD), a pyrimidine-degrading enzyme, was highly expressed upon EMT induction and was necessary for cells to acquire mesenchymal characteristics in vitro and for tumorigenic cells to extravasate into the mouse lung. This role of DPYD was mediated through its catalytic activity and enzymatic products, the dihydropyrimidines. Thus, we identify metabolic processes essential for the EMT, a program associated with the acquisition of metastatic and aggressive cancer cell traits.
Authors:
Yoav D Shaul; Elizaveta Freinkman; William C Comb; Jason R Cantor; Wai Leong Tam; Prathapan Thiru; Dohoon Kim; Naama Kanarek; Michael E Pacold; Walter W Chen; Brian Bierie; Richard Possemato; Ferenc Reinhardt; Robert A Weinberg; Michael B Yaffe; David M Sabatini
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cell     Volume:  158     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-08-30     Completed Date:  -     Revised Date:  2014-12-02    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1094-109     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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Grant Support
ID/Acronym/Agency:
AI047389/AI/NIAID NIH HHS; K99 CA168940/CA/NCI NIH HHS; R01 CA103866/CA/NCI NIH HHS; R01 CA103866/CA/NCI NIH HHS; R37 AI047389/AI/NIAID NIH HHS
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