ArticleProceedings of the National Academy of Sciences of the United States of America2013
Hypoxia induces a phase transition within a kinase signaling network in cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed.
- Clinically relevant glioblastoma patient-derived xenograft models to guide drug development and identify molecular signatures.Frontiers in oncology · 2023Article
- Del-1 enhances therapeutic efficacy of bacterial cancer immunotherapy by blocking recruitment of tumor-infiltrating neutrophils.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Microfluidic Single-Cell Proteomics Assay Chip: Lung Cancer Cell Line Case Study.Micromachines · 2021Article
- Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.Cell reports · 2021Article
- Single-cell proteomic analysis.WIREs mechanisms of disease · 2021Review
- Deep Profiling of Cellular Heterogeneity by Emerging Single-Cell Proteomic Technologies.Proteomics · 2020Review
- Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line.Nature communications · 2020Article
- Attenuated Salmonella engineered with an apoptosis-inducing factor (AIF) eukaryotic expressing system enhances its anti-tumor effect in melanoma in vitro and in vivo.Applied microbiology and biotechnology · 2020Article
- Intracellular redox potential is correlated with miRNA expression in MCF7 cells under hypoxic conditions.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance.PLoS computational biology · 2019Article
- Highly Multiplexed Single-Cell Protein Profiling with Large-Scale Convertible DNA-Antibody Barcoded Arrays.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2018Article
- Microchip-based single-cell functional proteomics for biomedical applications.Lab on a chip · 2017Review
- Understanding cell signaling in cancer stem cells for targeted therapy - can phosphoproteomics help to reveal the secrets?Cell communication and signaling : CCS · 2017Review
- Single cell proteomics in biomedicine: High-dimensional data acquisition, visualization, and analysis.Proteomics · 2017Review
- Exploiting receptor tyrosine kinase co-activation for cancer therapy.Drug discovery today · 2017Review
- Single-Cell, Multiplexed Protein Detection of Rare Tumor Cells Based on a Beads-on-Barcode Antibody Microarray.Analytical chemistry · 2016Article
- Targeted Cancer Therapy Using Engineered Salmonella typhimurium.Chonnam medical journal · 2016Review
- Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells.Scientific reports · 2016Article
- Recent Progress of Microfluidics in Translational Applications.Advanced healthcare materials · 2016Review
- Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma.Cancer cell · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)--a critical component of hypoxic signaling and a compelling cancer drug target--is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier's principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles.
Indexed as
Identifiers
What OpenQuestion holds
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.