ReviewThe international journal of biochemistry & cell biology2011
Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment.
Review in The international journal of biochemistry & cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.
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
149 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hotspots and Frontiers in Inflammatory Tumor Microenvironment Research: A Scientometric and Visualization Analysis.Frontiers in pharmacology · 2022Pooled it
- Trial
- Systemic Inflammation, Tumor Isotopic Signatures, and Prognosis in Oral Squamous Cell Carcinoma: Exploratory Integration of Blood- and Tissue-Derived Biomarkers-An Exploratory Retrospective Secondary Analysis.Journal of clinical medicine · 2026Article
- Small extracellular vesicles in tumor metabolism and immune escape: biomarkers and therapeutic opportunities.Molecular biology reports · 2026Review
- Exploring the role of protein homeostasis regulation in glycolysis in head and neck tumors.Human cell · 2026Review
- The Role of Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in the Tumor Microenvironment and Their Impact on Ovarian Cancer Survival and Therapy.Current oncology (Toronto, Ont.) · 2026Review
- Therapy-imprinted fibroblast memory in cholangiocarcinoma: rewiring CAF niches for immune evasion and treatment-resistant relapse.Frontiers in immunology · 2026Review
- Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.Journal of physiology and biochemistry · 2025Review
- Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications.Medical oncology (Northwood, London, England) · 2024Review
- Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies.Cell communication and signaling : CCS · 2024Review
- Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring.Cancer cell · 2023Article
- The biological function of tumor-derived extracellular vesicles on metabolism.Cell communication and signaling : CCS · 2023Review
- A Phase I Dose-escalation Study of AZD3965, an Oral Monocarboxylate Transporter 1 Inhibitor, in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Extracellular Vesicles in Breast Cancer: From Biology and Function to Clinical Diagnosis and Therapeutic Management.International journal of molecular sciences · 2023Review
- Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis.International journal of molecular sciences · 2023Review
- TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.Journal of hematology & oncology · 2022Review
- Upregulation of Nox4 induces a pro-survival Nrf2 response in cancer-associated fibroblasts that promotes tumorigenesis and metastasis, in part via Birc5 induction.Breast cancer research : BCR · 2022Article
- Review
- Altered RBP1 Gene Expression Impacts Epithelial Cell Retinoic Acid, Proliferation, and Microenvironment.Cells · 2022Article
- Monocarboxylate Transporter 4 in Cancer-Associated Fibroblasts Is a Driver of Aggressiveness in Aerodigestive Tract Cancers.Frontiers in oncology · 2022Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in "cancer cell nests" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are "parasites" that use oxidative stress as a "weapon" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to "feed" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm "The Autophagic Tumor Stroma Model of Cancer Metabolism", or the "Reverse Warburg Effect". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.
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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.