title: Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth.
abstract: Cancer cells rely on aerobic glycolysis to maintain cell growth and proliferation via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the first step of the serine biosynthetic pathway downstream of glycolysis, which is a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent DNA synthesis. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer cell lines. PHGDH knockdown in these cells leads to a reduction of serine synthesis and impairment of cancer cell proliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established breast cancer xenograft models, suggesting that PHGDH-dependent cancer cell growth may be context-dependent. Our findings suggest that other mechanisms or pathways may bypass exclusive dependence on PHGDH in established human breast cancer xenografts, indicating that PHGDH is dispensable for the growth and maintenance and of tumors in vivo.
authors: Oncology, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, United States.
authors: Jinyun
authors: J
authors: Chen
authors: Franklin
authors: F
authors: Chung
authors: Guizhi
authors: G
authors: Yang
authors: Minying
authors: M
authors: Pu
authors: Hui
authors: H
authors: Gao
authors: Wei
authors: W
authors: Jiang
authors: Hong
authors: H
authors: Yin
authors: Vladimir
authors: V
authors: Capka
authors: Shailaja
authors: S
authors: Kasibhatla
authors: Bryan
authors: B
authors: Laffitte
authors: Savina
authors: S
authors: Jaeger
authors: Raymond
authors: R
authors: Pagliarini
authors: Yaoyu
authors: Y
authors: Chen
authors: Wenlai
authors: W
authors: Zhou
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D050543:Phosphoglycerate Dehydrogenase