ArticleCell death and differentiation2019
The mitochondrial retrograde signaling regulates Wnt signaling to promote tumorigenesis in colon cancer.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 83 citations in OpenAlex.
- c-Fos-driven metabolic switch of α-ketoglutarate orchestrates progression in prostate cancer.Cell death & disease · 2026Article
- Re-evaluating the rationale for targeting oxidative phosphorylation in acute myeloid leukemia.The Biochemical journal · 2026Review
- Mitochondrial AK3 inhibits nuclear β-catenin localization and its activation through enhancing mitochondrial activity.Cell death & disease · 2026Article
- Mitochondrial function meets oncology: the multifaceted role of TFAM across cancer types.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- SIRT6-Mediated Regulation of TFAM: A Central Mechanism Connecting Nuclear and Mitochondrial Transcriptional Processes and Mitophagy.International journal of biological sciences · 2026Article
- Mitochondrial unfolded protein response as a central stress-integration hub: mechanisms and implications in disease contexts.Burns & trauma · 2026Review
- Chlorogenic acid promotes mtDNA leakage to enhance cGAS-STING induced anti-tumor immunity via ATF5-mtHSP70-TFAM system.International journal of biological sciences · 2026Article
- Mitochondrial retrograde signaling in gastric cancer: mtDNA mutations, ROS-driven NF-κB/HIF-1α activation, and Warburg effect amplification.Frontiers in physiology · 2026Review
- Integrated Single-cell Analysis Uncovers Regulatory Logic of Cranial Ectoderm Development.bioRxiv : the preprint server for biology · 2025Article
- mTORC1-USP30-LEF1 Cascade Regulates Cancer Stemness and Malignant Progression Through Mitonuclear Crosstalk.MedComm · 2025Article
- Integrated control of cancer stemness by σOncogene · 2025Article
- Regulatory effect of Wnt signaling on mitochondria in cancer: from mechanism to therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment.Cell reports. Medicine · 2025Article
- Total cardiolipin levels in gastric and colon cancer: evaluating the prognostic potential.Lipids in health and disease · 2025Article
- Crosstalk between dysregulated amino acid sensing and glucose and lipid metabolism in colorectal cancer.Frontiers in oncology · 2025Review
- Characterization of the stem cell landscape and identification of a stemness-associated prognostic signature in bladder cancer.Cancer cell international · 2024Article
- Mitochondrial function and gastrointestinal diseases.Nature reviews. Gastroenterology & hepatology · 2024Review
- ETV2 regulating PHD2-HIF-1α axis controls metabolism reprogramming promotes vascularized bone regeneration.Bioactive materials · 2024Article
- Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer cells are known to upregulate aerobic glycolysis to promote growth, proliferation, and survival. However, the role of mitochondrial respiration in tumorigenesis remains elusive. Here we report that inhibition of mitochondrial function by silencing TFAM, a key transcription factor essential for mitochondrial DNA (mtDNA) replication and the transcription of mtDNA-encoded genes, markedly reduced tumor-initiating potential of colon cancer cells. Knockdown of TFAM significantly decreased mitochondrial respiration in colon cancer cells; however, the cellular levels of ATP remained largely unchanged as a result of increased glycolysis. This metabolic alteration rendered cancer cells highly susceptible to glucose deprivation. Interestingly, upregulation of glycolysis was independent of hypoxia-inducible factor-1 (HIF1) as TFAM knockdown cells fail to stabilize HIF1α under hypoxic conditions. Moreover, knockdown of TFAM results in decreased expression of genes-associated cancer stem cells downstream of Wnt/β-catenin signaling. Metabolic analysis reveals that the level of α-ketoglutarate (α-KG) was significantly upregulated in TFAM knockout cells. Silencing of prolyl hydroxylase domain-containing protein 2 (PHD2), a α-KG-dependent dioxyenase, rescued the expression of target genes of both HIF1α and Wnt/β-catenin. Furthermore, intestinal-specific knockout of TFAM prevents tumor formation in Apc-mutant mouse models of colon cancer. Taken together, our findings identify a novel role of mitochondria-mediated retrograde signaling in regulating Wnt signaling and tumor initiation in colon cancer.
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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.