Abstract：
:Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Zielinski DC,Jamshidi N,Corbett AJ,Bordbar A,Thomas A,Palsson BOdoi
10.1038/srep41241subject
Has Abstractpub_date
2017-01-25 00:00:00pages
41241issn
2045-2322pii
srep41241journal_volume
7pub_type
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