Mitochondria preserve an autarkic one-carbon cycle to confer growth-independent cancer cell migration and metastasis.

ABSTRACT: Metastasis is the most common cause of death in cancer patients. Canonical drugs target mainly the proliferative capacity of cancer cells, which leaves slow-proliferating, persistent cancer cells unaffected. Metabolic determinants that contribute to growth-independent functions are still poorly understood. Here we show that antifolate treatment results in an uncoupled and autarkic mitochondrial one-carbon (1C) metabolism during cytosolic 1C metabolism impairment. Interestingly, antifolate dependent growth-arrest does not correlate with decreased migration capacity. Therefore, using methotrexate as a tool compound allows us to disentangle proliferation and migration to profile the metabolic phenotype of migrating cells. We observe that increased serine de novo synthesis (SSP) supports mitoc

SUBMITTER: Kiweler N 

PROVIDER: S-EPMC9110368 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature