ArticleCancer research2011
Frequent truncating mutation of TFAM induces mitochondrial DNA depletion and apoptotic resistance in microsatellite-unstable colorectal cancer.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 107 citations in OpenAlex.
- Mitochondrial function meets oncology: the multifaceted role of TFAM across cancer types.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondrial complex I in focus: mechanisms and therapeutic strategies of urinary system diseases.Frontiers in physiology · 2026Review
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Comprehensive analysis of Mendelian randomization and scRNA-seq identify key prognostic genes and relevant functional roles in colorectal cancer.Scientific reports · 2025Article
- Oxidized Low-Density Lipoprotein as a Potential Target for Enhancing Immune Checkpoint Inhibitor Therapy in Microsatellite-Stable Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- FoxM1 promotes TFAM expression and regulates Mitochondrial Dynamics in Glioblastoma cells.Journal of Cancer · 2025Article
- Targeting the epigenome and tumor heterogeneity: advances in immunotherapy for chemoresistant metastatic colorectal cancer.Frontiers in immunology · 2025Review
- Decreased mitochondrial transcription factor A and mitochondrial DNA copy number promote cyclin-dependent kinase inhibitor 1A expression and reduce tumorigenic properties of colorectal cancer cells.Discover oncology · 2024Article
- Mitochondria transcription and cancer.Cell death discovery · 2024Review
- Mitochondrial DNA copy number plays opposing roles in T-lymphocyte infiltration of colorectal cancer based on mismatch repair status: new directions for immunotherapy?British journal of cancer · 2024Article
- Mitochondrial Deoxyribonucleic Acid Copy Number Elevation As a Predictor for Extended Survival and Favorable Outcomes in High-Grade Brain Tumor Patients: A Malaysian Study.The Eurasian journal of medicine · 2024Article
- Mitochondria: a crucial factor in the progression and drug resistance of colorectal cancer.Frontiers in immunology · 2024Review
- ZNF281 inhibits mitochondrial biogenesis to facilitate metastasis of hepatocellular carcinoma.Cell death discovery · 2023Article
- Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Mitochondria-RelatedGenes · 2023Article
- Therapeutic effects of sulforaphane in ulcerative colitis: effect on antioxidant activity, mitochondrial biogenesis and DNA polymerization.Redox report : communications in free radical research · 2022Article
- Gemcitabine Resistance in Pancreatic Ductal Carcinoma Cell Lines Stems from Reprogramming of Energy Metabolism.International journal of molecular sciences · 2022Article
- Low-dose sodium-glucose cotransporter 2 inhibitor ameliorates ischemic brain injury in mice through pericyte protection without glucose-lowering effects.Communications biology · 2022Article
- Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA (mtDNA) replication and transcription. Disruption of TFAM results in heart failure and premature aging in mice. But very little is known about the role of TFAM in cancer development. Here, we report the identification of frequent frameshift mutations in the coding mononucleotide repeat of TFAM in sporadic colorectal cancer (CRC) cell lines and in primary tumors with microsatellite instability (MSI), but not in microsatellite stable (MSS) CRC cell lines and tumors. The presence of the TFAM truncating mutation, in CRC cells with MSI, reduced the TFAM protein level in vivo and in vitro and correlated with mtDNA depletion. Furthermore, forced overexpression of wild-type TFAM in RKO cells carrying a TFAM truncating mutation suppressed cell proliferation and inhibited RKO cell-induced xenograft tumor growth. Moreover, these cells showed more susceptibility to cisplatin-induced apoptosis due to an increase of cytochrome b (Cyt b) expression and its release from mitochondria. An interaction assay between TFAM and the heavy-strand promoter (HSP) of mitochondria revealed that mutant TFAM exhibited reduced binding to HSP, leading to reduction in Cyt b transcription. Collectively, these data provide evidence that a high incidence of TFAM truncating mutations leads to mitochondrial copy number reduction and mitochondrial instability, distinguishing most CRC with MSI from MSS CRC. These mutations may play an important role in tumorigenesis and cisplatin-induced apoptotic resistance of most microsatellite-unstable CRCs.
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