Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2019 Mar 18;35(3):339-341.
doi: 10.1016/j.ccell.2019.02.014.

Serine and Methionine Metabolism: Vulnerabilities in Lethal Prostate Cancer

Xia Gao  1 , Jason W Locasale  2 , Michael A Reid  1
Affiliations
Comment

Serine and Methionine Metabolism: Vulnerabilities in Lethal Prostate Cancer

Xia Gao et al. Cancer Cell. .

Abstract

Altered metabolism is a common feature of new and recurring malignancy. In this issue of Cancer Cell, Reina-Campos and colleagues report upregulation of the serine, glycine, one-carbon (SGOC) metabolic network is required for neuroendocrine prostate cancer, a castration-resistant aggressive form of the disease, and presents a targetable vulnerability.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Schematic of how SGOC metabolism creates a vulnerability in NEPC.
Downregulation of protein kinase C (PKC)λ/ι in neuroendocrine prostate cancer (NEPC) leads to rewiring of the serine, glycine, one-carbon (SGOC) metabolic network through an mTORC1/ATF4-dependent pathway. The upregulation of de novo serine biosynthesis results in increased intracellular S-Adenosylmethionine (SAM) levels that alters DNA methylation status and supports the development of NEPC. PC-Adeno (Prostate adenocarcinoma); DNMTs (DNA methyltransferases); PHGDH (phosphoglycerate dehydrogenase); PSAT1 (phosphoserine aminotransferase 1); Ser (serine).
See this image and copyright information in PMC

Comment on

References

    1. Deblois G, Tonekaboni SAM, Kao Y, Tai F, Liu X, Ettayebi I, Grillo G, Guilhamon P, Ba-alawi W, Fedor A, et al. (2018). Metabolic adaptations underlie epigenetic vulnerabilities in chemoresistant breast cancer. bioRxiv (Preprint).
    1. Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu H, Nagle JM, Boukhali M, Hayward MC, Li YY, Chen T , et al. (2016). LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 539, 390–395. - PMC - PubMed
    1. Ku SY, Rosario S, Wang Y, Mu P, Seshadri M, Goodrich ZW, Goodrich MM, Labbe DP, Gomez EC, Wang J , et al. (2017). Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355, 78–83. - PMC - PubMed
    1. Luengo A, Gui DY, and Vander Heiden MG (2017). Targeting Metabolism for Cancer Therapy. Cell Chem Biol 24, 1161–1180. - PMC - PubMed
    1. Ma L, Tao Y, Duran A, Llado V, Galvez A, Barger JF, Castilla EA, Chen J, Yajima T, Porollo A, et al. (2013). Control of nutrient stress-induced metabolic reprogramming by PKCzeta in tumorigenesis. Cell 152, 599–611. - PMC - PubMed

Publication types