ArticleScientific reports2018
Shift from stochastic to spatially-ordered expression of serine-glycine synthesis enzymes in 3D microtumors.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- PHGDH mediated serine biosynthesis metabolism suppresses vascular calcification.Biology direct · 2026Article
- PHGDH: a novel therapeutic target in cancer.Experimental & molecular medicine · 2024Review
- Bridging systems biology and tissue engineering: Unleashing the full potential of complex 3DBiophysics reviews · 2024Review
- Breast cancers as ecosystems: a metabolic perspective.Cellular and molecular life sciences : CMLS · 2023Review
- Discovery of Myeloid-Derived Suppressor Cell-Specific Metabolism by Metabolomic and Lipidomic Profiling.Metabolites · 2023Article
- Serine-associated one-carbon metabolic reprogramming: a new anti-cancer therapeutic strategy.Frontiers in oncology · 2023Review
- Metabolic Flexibility Is a Determinant of Breast Cancer Heterogeneity and Progression.Cancers · 2021Review
- Interplay between tumor microenvironment and partial EMT as the driver of tumor progression.iScience · 2021Review
- Three dimensional engineered models to study hypoxia biology in breast cancer.Cancer letters · 2020Review
- Modeling HIV-1 neuropathogenesis using three-dimensional human brain organoids (hBORGs) with HIV-1 infected microglia.Scientific reports · 2020Article
- PHGDH as a mechanism for resistance in metabolically-driven cancers.Cancer drug resistance (Alhambra, Calif.) · 2020Article
- Targeting the Temporal Dynamics of Hypoxia-Induced Tumor-Secreted Factors Halts Tumor Migration.Cancer research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Cell-to-cell differences in protein expression in normal tissues and tumors are a common phenomenon, but the underlying principles that govern this heterogeneity are largely unknown. Here, we show that in monolayer cancer cell-line cultures, the expression of the five metabolic enzymes of serine-glycine synthesis (SGS), including its rate-limiting enzyme, phosphoglycerate dehydrogenase (PHGDH), displays stochastic cell-to-cell variation. By contrast, in cancer cell line-derived three-dimensional (3D) microtumors PHGDH expression is restricted to the outermost part of the microtumors' outer proliferative cell layer, while the four other SGS enzymes display near uniform expression throughout the microtumor. A mathematical model suggests that metabolic stress in the microtumor core activates factors that restrict PHGDH expression. Thus, intracellular enzyme expression in growing cell ecosystems can shift to spatially ordered patterns in 3D structured environments due to emergent cell-cell communication, with potential implications for the design of effective anti-metabolic cancer therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.