Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition
- Description
Brain metastasis is the most common intracranial malignancy in adults, which is often fatal. This study showed that 3-phosphoglycerate dehydrogenase (PHGDH), which catalyzes the rate limiting step of glucose derived serine synthesis, is a major determinant of brain metastasis. For the study, proteomes and labeled metabolomes of parental, aggressive, and indolent TNBC brain metastatic (BrM) cells were analyzed to gain insight into the molecular events underlying brain metastasis. To investigate the potential mechanisms responsible for reduced cell growth in limited-serine microenvironments following PHGDH inhibition, comparative phospho-proteomics was performed on PHGDH depleted aggressive TNBC BrM cells. In addition, aggressive and indolent TNBC BrM cells were cultured with uniformly carbon-labeled 13C glucose and the mole percent enrichment of glucose-derived metabolites were measured to understand the metabolic consequences of increased PHGDH expression in brain metastasis. The dataset contains proteomic and metabolomic data.
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- Grant Support
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Career Awards for Medical Scientists/Burroughs Wellcome FundStarr Cancer Consortium/Starr Cancer ConsortiumHHMI Faculty Scholars/Howard Hughes Medical InstituteNSF Graduate Research Fellowship/National Science FoundationRobertson Foundation/Robertson FoundationMedical Research Fellows Program/Howard Hughes Medical InstituteTow Foundation Fellowship Program/Center for Molecular Imaging and BioengineeringParker Institute for Cancer Immunotherapy/Memorial Sloan Kettering Cancer CenterW81XWH-16-1-0315/Department of DefenseCaroline Ross Endowment Fellowship/University of Texas MD Anderson Cancer CenterSchissler Foundation Fellowship/University of Texas MD Anderson Cancer CenterPresidents’ Research Scholarship/University of Texas MD Anderson Cancer CenterDonald E. and Delia B. Baxter Foundation/Donald E. and Delia B. Baxter FoundationPrevent Cancer Foundation/Prevent Cancer FoundationWright Foundation/Wright FoundationPew-Stewart Scholars for Cancer Research/Pew Charitable TrustsW81XWH-18-1-0491/Department of DefenseBreast Cancer Research Foundation/Breast Cancer Research FoundationDr. Miriam and Sheldon G. Adelson Medical Research Foundation/Dr. Miriam and Sheldon G. Adelson Medical Research FoundationAIM at Melanoma Foundation/AIM at Melanoma FoundationRP170401/Cancer Prevention and Research Institute of TexasRP160183/Cancer Prevention and Research Institute of TexasMultidisciplinary Reconstruction Research Program/University of Texas MD Anderson Cancer CenterMelanoma Moon Shot Program/University of Texas MD Anderson Cancer CenterDana-Farber Harvard Cancer Center/Dana-Farber Harvard Cancer CenterKoch Institute Bridge Project/Massachusetts Institute of TechnologyLustgarten Foundation/Lustgarten FoundationHU Ludwig Center/Harvard UniversityW81XWH-10-1-0016/Department of DefenseMIT Ludwig Center/Massachusetts Institute of TechnologyCenter for Precision Cancer Medicine/Massachusetts Institute of TechnologyStand Up To Cancer Innovative Research Grant/American Association for Cancer ResearchMax Planck Society for the Advancement of Science/Max Planck Society for the Advancement of ScienceHorizon 2020/European Union7th Framework Programme for Research/European UnionCenter for Protein Research/Novo Nordisk FoundationBasser Initiative/Gray FoundationLori and Zachary Schreiber Family Fund/Schreiber Family FoundationRoger and Susan Hertog Fund/Hertog FoundationCancer Research Grant/Mary Kay FoundationShifrin-Myers Breast Cancer Discovery Fund/NYU Langone Medical CenterV Foundation V Scholar Award/Hearst FoundationMRA Young Investigator Award/Tara Miller Melanoma FoundationJohn and Elaine Kanas Family Foundation/John and Elaine Kanas Family FoundationCenter for Biospecimen Research and Development/NYU Langone Medical CenterMetabolomics Laboratory/NYU Langone HealthCancer Center Support Grant/NYU Perlmutter Cancer Center