학술논문

Targeting one-carbon metabolism requires mTOR inhibition: a new therapeutic approach in osteosarcoma
Document Type
article
Source
Molecular & Cellular Oncology, Vol 8, Iss 3 (2021)
Subject
phgdh
serine
osteosarcoma
methotrexate
mtorc1
perhexiline
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
2372-3556
23723556
Abstract
The rate-limiting enzyme of serine biosynthesis, 3-phosphoglycerate dehydrogenase (PHGDH), contributes to rapid growth and proliferation when it is overexpressed in cancer. We recently described the metabolic adaptations that occur upon PHGDH inhibition in osteosarcoma. PHGDH inhibition causes metabolite accumulation that activates the mechanistic target of rapamycin (mTOR) signaling, sensitizing osteosarcoma to non-rapalog mTOR inhibition.