Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition

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Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition. / Ngo, Bryan; Kim, Eugenie; Osorio-Vasquez, Victoria; Doll, Sophia; Bustraan, Sophia; Liang, Roger J; Luengo, Alba; Davidson, Shawn M; Ali, Ahmed; Ferraro, Gino B; Fischer, Grant M; Eskandari, Roozbeh; Kang, Diane S; Ni, Jing; Plasger, Ariana; Rajasekhar, Vinagolu K; Kastenhuber, Edward R; Bacha, Sarah; Sriram, Roshan K; Stein, Benjamin D; Bakhoum, Samuel F; Snuderl, Matija; Cotzia, Paolo; Healey, John H; Mainolfi, Nello; Suri, Vipin; Friedman, Adam; Manfredi, Mark; Sabatini, David M; Jones, Drew R; Yu, Min; Zhao, Jean J; Jain, Rakesh K; Keshari, Kayvan R; Davies, Michael A; Vander Heiden, Matthew G; Hernando, Eva; Mann, Matthias; Cantley, Lewis C; Pacold, Michael E.

In: Cancer Discovery, Vol. 10, No. 9, 2020, p. 1352-1373.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ngo, B, Kim, E, Osorio-Vasquez, V, Doll, S, Bustraan, S, Liang, RJ, Luengo, A, Davidson, SM, Ali, A, Ferraro, GB, Fischer, GM, Eskandari, R, Kang, DS, Ni, J, Plasger, A, Rajasekhar, VK, Kastenhuber, ER, Bacha, S, Sriram, RK, Stein, BD, Bakhoum, SF, Snuderl, M, Cotzia, P, Healey, JH, Mainolfi, N, Suri, V, Friedman, A, Manfredi, M, Sabatini, DM, Jones, DR, Yu, M, Zhao, JJ, Jain, RK, Keshari, KR, Davies, MA, Vander Heiden, MG, Hernando, E, Mann, M, Cantley, LC & Pacold, ME 2020, 'Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition', Cancer Discovery, vol. 10, no. 9, pp. 1352-1373. https://doi.org/10.1158/2159-8290.CD-19-1228

APA

Ngo, B., Kim, E., Osorio-Vasquez, V., Doll, S., Bustraan, S., Liang, R. J., Luengo, A., Davidson, S. M., Ali, A., Ferraro, G. B., Fischer, G. M., Eskandari, R., Kang, D. S., Ni, J., Plasger, A., Rajasekhar, V. K., Kastenhuber, E. R., Bacha, S., Sriram, R. K., ... Pacold, M. E. (2020). Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition. Cancer Discovery, 10(9), 1352-1373. https://doi.org/10.1158/2159-8290.CD-19-1228

Vancouver

Ngo B, Kim E, Osorio-Vasquez V, Doll S, Bustraan S, Liang RJ et al. Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition. Cancer Discovery. 2020;10(9):1352-1373. https://doi.org/10.1158/2159-8290.CD-19-1228

Author

Ngo, Bryan ; Kim, Eugenie ; Osorio-Vasquez, Victoria ; Doll, Sophia ; Bustraan, Sophia ; Liang, Roger J ; Luengo, Alba ; Davidson, Shawn M ; Ali, Ahmed ; Ferraro, Gino B ; Fischer, Grant M ; Eskandari, Roozbeh ; Kang, Diane S ; Ni, Jing ; Plasger, Ariana ; Rajasekhar, Vinagolu K ; Kastenhuber, Edward R ; Bacha, Sarah ; Sriram, Roshan K ; Stein, Benjamin D ; Bakhoum, Samuel F ; Snuderl, Matija ; Cotzia, Paolo ; Healey, John H ; Mainolfi, Nello ; Suri, Vipin ; Friedman, Adam ; Manfredi, Mark ; Sabatini, David M ; Jones, Drew R ; Yu, Min ; Zhao, Jean J ; Jain, Rakesh K ; Keshari, Kayvan R ; Davies, Michael A ; Vander Heiden, Matthew G ; Hernando, Eva ; Mann, Matthias ; Cantley, Lewis C ; Pacold, Michael E. / Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition. In: Cancer Discovery. 2020 ; Vol. 10, No. 9. pp. 1352-1373.

Bibtex

@article{d3221fcf632041449c1f5c5ca8c0e97d,
title = "Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition",
abstract = "A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine-limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types and preclinical models. Enhanced serine synthesis proved important for nucleotide production and cell proliferation in highly aggressive brain metastatic cells. In vivo, genetic suppression and pharmacological inhibition of PHGDH attenuated brain metastasis, but not extracranial tumor growth, and improved overall survival in mice. These results reveal that extracellular amino acid availability determines serine synthesis pathway dependence, and suggests that PHGDH inhibitors may be useful in the treatment of brain metastasis.",
author = "Bryan Ngo and Eugenie Kim and Victoria Osorio-Vasquez and Sophia Doll and Sophia Bustraan and Liang, {Roger J} and Alba Luengo and Davidson, {Shawn M} and Ahmed Ali and Ferraro, {Gino B} and Fischer, {Grant M} and Roozbeh Eskandari and Kang, {Diane S} and Jing Ni and Ariana Plasger and Rajasekhar, {Vinagolu K} and Kastenhuber, {Edward R} and Sarah Bacha and Sriram, {Roshan K} and Stein, {Benjamin D} and Bakhoum, {Samuel F} and Matija Snuderl and Paolo Cotzia and Healey, {John H} and Nello Mainolfi and Vipin Suri and Adam Friedman and Mark Manfredi and Sabatini, {David M} and Jones, {Drew R} and Min Yu and Zhao, {Jean J} and Jain, {Rakesh K} and Keshari, {Kayvan R} and Davies, {Michael A} and {Vander Heiden}, {Matthew G} and Eva Hernando and Matthias Mann and Cantley, {Lewis C} and Pacold, {Michael E}",
note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",
year = "2020",
doi = "10.1158/2159-8290.CD-19-1228",
language = "English",
volume = "10",
pages = "1352--1373",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research",
number = "9",

}

RIS

TY - JOUR

T1 - Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition

AU - Ngo, Bryan

AU - Kim, Eugenie

AU - Osorio-Vasquez, Victoria

AU - Doll, Sophia

AU - Bustraan, Sophia

AU - Liang, Roger J

AU - Luengo, Alba

AU - Davidson, Shawn M

AU - Ali, Ahmed

AU - Ferraro, Gino B

AU - Fischer, Grant M

AU - Eskandari, Roozbeh

AU - Kang, Diane S

AU - Ni, Jing

AU - Plasger, Ariana

AU - Rajasekhar, Vinagolu K

AU - Kastenhuber, Edward R

AU - Bacha, Sarah

AU - Sriram, Roshan K

AU - Stein, Benjamin D

AU - Bakhoum, Samuel F

AU - Snuderl, Matija

AU - Cotzia, Paolo

AU - Healey, John H

AU - Mainolfi, Nello

AU - Suri, Vipin

AU - Friedman, Adam

AU - Manfredi, Mark

AU - Sabatini, David M

AU - Jones, Drew R

AU - Yu, Min

AU - Zhao, Jean J

AU - Jain, Rakesh K

AU - Keshari, Kayvan R

AU - Davies, Michael A

AU - Vander Heiden, Matthew G

AU - Hernando, Eva

AU - Mann, Matthias

AU - Cantley, Lewis C

AU - Pacold, Michael E

N1 - Copyright ©2020, American Association for Cancer Research.

PY - 2020

Y1 - 2020

N2 - A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine-limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types and preclinical models. Enhanced serine synthesis proved important for nucleotide production and cell proliferation in highly aggressive brain metastatic cells. In vivo, genetic suppression and pharmacological inhibition of PHGDH attenuated brain metastasis, but not extracranial tumor growth, and improved overall survival in mice. These results reveal that extracellular amino acid availability determines serine synthesis pathway dependence, and suggests that PHGDH inhibitors may be useful in the treatment of brain metastasis.

AB - A hallmark of metastasis is the adaptation of tumor cells to new environments. Metabolic constraints imposed by the serine and glycine-limited brain environment restrict metastatic tumor growth. How brain metastases overcome these growth-prohibitive conditions is poorly understood. Here, we demonstrate that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate-limiting step of glucose-derived serine synthesis, is a major determinant of brain metastasis in multiple human cancer types and preclinical models. Enhanced serine synthesis proved important for nucleotide production and cell proliferation in highly aggressive brain metastatic cells. In vivo, genetic suppression and pharmacological inhibition of PHGDH attenuated brain metastasis, but not extracranial tumor growth, and improved overall survival in mice. These results reveal that extracellular amino acid availability determines serine synthesis pathway dependence, and suggests that PHGDH inhibitors may be useful in the treatment of brain metastasis.

U2 - 10.1158/2159-8290.CD-19-1228

DO - 10.1158/2159-8290.CD-19-1228

M3 - Journal article

C2 - 32571778

VL - 10

SP - 1352

EP - 1373

JO - Cancer Discovery

JF - Cancer Discovery

SN - 2159-8274

IS - 9

ER -

ID: 243473535