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Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth

Chen, Jinyun and Chung, Franklin and Yang, Guizhi and Pu, Minying and Gao, Hui and Jiang, Wei and Yin, Hong and Capka, Vladimir and Kasibhatla, Shailaja and Laffitte, Bryan and Pagliarini, Raymond and Chen, Yaoyu and Zhou, Wenlai (2013) Phosphoglycerate dehydrogenase is dispensable for breast tumor maintenance and growth. Oncotarget, 4 (12). pp. 2502-2511. ISSN 1949-2553

Abstract

Cancer cells have the ability to use aerobic glycolysis to maintain cell growth and proliferation via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the first step of the serine biosynthetic pathway, which is a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent DNA synthesis. PHGDH is amplified or overexpressed in a subset of breast cancer and melanoma, and critical for the viability of those cells. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer cell lines and PHGDH knockdown in these cells leads to a decrease in the levels of serine production and impairment of cancer cell proliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established xenograft tumor mouse models, suggesting that PHGDH-dependent cell growth is only observed in the in vitro context. Our finding indicates that PHGDH is dispensable for tumor maintenance and growth in vivo, which suggests that other mechanisms or pathways may bypass the function of PHGDH in human breast cancer cells.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/10793

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