ArticleMolecular systems biology2017
Mathematical modeling links Wnt signaling to emergent patterns of metabolism in colon cancer.
Article in Molecular systems biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 46 citations in OpenAlex.
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- Tissue stiffness heterogeneity in the jaw and temporomandibular joint: its impact on tumor metabolism and considerations forFrontiers in physiology · 2025Review
- Canonical WNT/β-catenin signaling upregulates aerobic glycolysis in diverse cancer types.Molecular biology reports · 2024Review
- Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high.BMC cancer · 2024Article
- Colorectal Cancer Stem Cell Subtypes Orchestrate Distinct Tumor Microenvironments.bioRxiv : the preprint server for biology · 2024Article
- The DUX4-HIF1α Axis in Murine and Human Muscle Cells: A Link More Complex Than Expected.International journal of molecular sciences · 2024Article
- A Systems Biology Approach to Understand the Racial Disparities in Colorectal Cancer.Cancer research communications · 2024Article
- PRI-724 and IWP-O1 Wnt Signaling Pathway Inhibitors Modulate the Expression of Glycolytic Enzymes in Tongue Cancer Cell Lines.Current issues in molecular biology · 2023Article
- Stochastic modeling of the mRNA life process: A generalized master equation.Biophysical journal · 2023Article
- The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.Life (Basel, Switzerland) · 2023Review
- Data-driven spatio-temporal modelling of glioblastoma.Royal Society open science · 2023Review
- Modeling of Tumor Growth with Input from Patient-Specific Metabolomic Data.Annals of biomedical engineering · 2022Article
- Disruption of β-Catenin-Dependent Wnt Signaling in Colon Cancer Cells Remodels the Microenvironment to Promote Tumor Invasion.Molecular cancer research : MCR · 2022Article
- Targeting Cancer Metabolism Plasticity with JX06 Nanoparticles via Inhibiting PDK1 Combined with Metformin for Endometrial Cancer Patients with Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics.Frontiers in immunology · 2022Review
- Personalised Medicine for Colorectal Cancer Using Mechanism-Based Machine Learning Models.International journal of molecular sciences · 2021Article
- Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy.International journal of molecular sciences · 2021Review
- Pyruvate dehydrogenase kinases (PDKs): an overview toward clinical applications.Bioscience reports · 2021Review
- Hypothesis: Caco-2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts.Journal of cellular and molecular medicine · 2018Article
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7 authors at 1 institution in 1 country.
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Abstract
Cell-intrinsic metabolic reprogramming is a hallmark of cancer that provides anabolic support to cell proliferation. How reprogramming influences tumor heterogeneity or drug sensitivities is not well understood. Here, we report a self-organizing spatial pattern of glycolysis in xenograft colon tumors where pyruvate dehydrogenase kinase (PDK1), a negative regulator of oxidative phosphorylation, is highly active in clusters of cells arranged in a spotted array. To understand this pattern, we developed a reaction-diffusion model that incorporates Wnt signaling, a pathway known to upregulate PDK1 and Warburg metabolism. Partial interference with Wnt alters the size and intensity of the spotted pattern in tumors and in the model. The model predicts that Wnt inhibition should trigger an increase in proteins that enhance the range of Wnt ligand diffusion. Not only was this prediction validated in xenograft tumors but similar patterns also emerge in radiochemotherapy-treated colorectal cancer. The model also predicts that inhibitors that target glycolysis or Wnt signaling in combination should synergize and be more effective than each treatment individually. We validated this prediction in 3D colon tumor spheroids.
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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.