ArticleOncogene2016
Disruption of cytochrome c oxidase function induces the Warburg effect and metabolic reprogramming.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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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.
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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.
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Who cites it
63 citing papers in PubMed, 97 citations in OpenAlex.
- Mitochondrial dynamics: A promising tool for personalized TNBC management.Genes & diseases · 2026Review
- The Warburg hypothesis and the emergence of the mitochondrial metabolic theory of cancer.Journal of bioenergetics and biomembranes · 2025Review
- Single-Cell Transcriptomics Uncovers Core Signature for Regulating Mitochondrial Homeostasis During Testicular Ageing.Cell proliferation · 2025Article
- miR-6126 modulates GRP78 to suppress the Warburg effect and mitochondrial dynamics in triple-negative breast cancer.International journal of medical sciences · 2025Article
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- Canonical WNT/β-catenin signaling upregulates aerobic glycolysis in diverse cancer types.Molecular biology reports · 2024Review
- Socialized mitochondria: mitonuclear crosstalk in stress.Experimental & molecular medicine · 2024Review
- Implications of ZNF334 gene in lymph node metastasis of lung SCC: potential bypassing of cellular senescence.Journal of translational medicine · 2024Article
- Effect of hypoxia‑HIF‑1α‑periostin axis in thyroid cancer.Oncology reports · 2024Article
- Bioenergetic alteration in gastrointestinal cancers: The good, the bad and the ugly.World journal of gastroenterology · 2023Review
- Cellular Adaptation Takes Advantage of Atavistic Regression Programs during Carcinogenesis.Cancers · 2023Review
- Mutations in Structural Genes of the Mitochondrial Complex IV May Influence Breast Cancer.Genes · 2023Article
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- Cysteine dioxygenase type 1 (CDO1): Its functional role in physiological and pathophysiological processes.Genes & diseases · 2023Review
- Genetics of enzymatic dysfunctions in metabolic disorders and cancer.Frontiers in oncology · 2023Review
- Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions.Aging and disease · 2022Article
- Computational epigenetic landscape analysis reveals association of CACNA1G-AS1, F11-AS1, NNT-AS1, and MSC-AS1 lncRNAs in prostate cancer progression through aberrant methylation.Scientific reports · 2022Article
- COX4-1 promotes mitochondrial supercomplex assembly and limits reactive oxide species production in radioresistant GBM.Cell stress · 2022Article
3 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
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of the electron transport chain component cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage-dependent growth and acquired invasive phenotypes. Disruption of the CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling includes activation of PI3-kinase, IGF1R and Akt, Ca2(+)-sensitive transcription factors and also TGFβ1, MMP16 and periostin, which are involved in oncogenic progression. Whole-genome expression analysis showed the upregulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mitochondrial DNA depletion, although distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be the hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in the CcO complex can potentially induce tumor progression.
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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.