Abstract:
:Oncogenic signals contribute to enhanced glycolysis and mTORC1 activity, leading to rapid cell proliferation in cancer. Regulation of glycolysis and mTORC1 by PI3K/Akt signaling is well established, but how KRAS-induced MEK signaling regulates these pathways remains poorly understood. Here, we report a role for MEK-driven lactate production in mTORC1 activation in KRAS-activated cells. KRAS/MEK-induced upregulation of the chicken ovalbumin upstream promoter transcriptional factor II (COUP-TFII) increases the expression of lactate dehydrogenase A (LDHA), resulting in lactate production and mTORC1 activation. Further, lactate inhibits the interaction of TSC2 and Rheb, leading to the cellular activation of mTORC1 irrespective of growth factor stimulation. These findings suggest that COUP-TFII is a novel oncogenic mediator, connecting KRAS signaling and glycolysis, and leading to mTORC1 activation and cellular growth.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Byun JK,Park M,Yun JW,Lee J,Kim JS,Cho SJ,Lee YM,Lee IK,Choi YK,Park KGdoi
10.15252/embr.201847451subject
Has Abstractpub_date
2019-06-01 00:00:00issue
6eissn
1469-221Xissn
1469-3178pii
embr.201847451journal_volume
20pub_type
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