Abstract：
: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.
journal_name
Celljournal_title
Cellauthors
Shaul YD,Freinkman E,Comb WC,Cantor JR,Tam WL,Thiru P,Kim D,Kanarek N,Pacold ME,Chen WW,Bierie B,Possemato R,Reinhardt F,Weinberg RA,Yaffe MB,Sabatini DMdoi
10.1016/j.cell.2014.07.032subject
Has Abstractpub_date
2014-08-28 00:00:00pages
1094-1109issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(14)00982-9journal_volume
158pub_type
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