Mitochondrial DNA mutations in human cancer

Part III. Molecular changes induced by high nitric oxide adaptation in human breast cancer cell line BT-20 (BT-20-HNO): a switch from aerobic to anaerobic metabolism

“…These cell lines provide a model system in which we can understand the molecular mechanisms involved to become adapted to NO. In addition, we have adapted a number of tumor cell line pairs arising from other anatomical sites [9,13,40,41] and have studied both cell line pairs using a number of cellular and molecular methods including: MTT viability assay, FACS, LDH leakage assay, DNA sequencing, DNA fragments cloning, qPCR, and Western blot analysis.…”

“…The mutation caused a substitution of an amino acid residue from leucine (L) to phenylalanine (F) in exon 6 of p53 gene reported decrease of mtDNA copy number of the HNO cells, when compared with the parent cells, suggests a mitochondrial "malignancy" in the tumor cell [8]. Previous works have linked mtDNA damage with cancer development, progression, and metastasis [40,41]. Studies using cytoplasmic hybrid (cybrid) technology to replace the endogenous mtDNA with another mtDNA mutant have shown that the mitochondrial genome damage might be associated with ROS production, apoptosis resistance, and increased metastasis [42,43].…”

Mitochondrial pyrimidine nucleotide carrier (PNC1) regulates mitochondrial biogenesis and the invasive phenotype of cancer cells

“…In this report we found that suppression of PNC1 in transformed cells leads to acquisition of a more aggressive phenotype because of an ROS-dependent EMT programme. Mitochondria, and specifically, mutations in mtDNA, have previously been implicated in cancer progression (reviewed in Brandon et al, 2006;Chatterjee et al, 2006). Transfer of mutated mtDNA from highly metastatic cell lines is sufficient to initiate a metastatic phenotype in non-metastatic cell lines by promoting mitochondrial ROS production (Ishikawa et al, 2008).…”

Mitochondrial respiratory defects promote the Warburg effect and cancer progression

“…Mitochondrial DNA (mtDNA) defects such as mutations, deletions, and loss of copy number that result in defective electron transport chain complexes have been reported in a wide variety of cancers. 1,2 The causal role of mitochondrial defects in tumor formation has not been established; however, using hybrid cell technology to replace endogenous mtDNA with that from tumor cell lines, the role of mtDNA mutations of Complex I, III, and V subunits in inducing tumorigenic cellular transformations has been demonstrated. [2][3][4] Moreover, defects in nuclear encoded mitochondrial proteins such as succinate dehydrogenase, fumarate hydratase, and isocitrate dehydrogenase have been shown to lead to accumulation of oncometabolites and are directly implicated in specific cancers.…”

“…Mutations in mtDNAcoded subunits of CcO have been reported in prostrate, colon, thyroid, and breast cancers. 1,2 Although some of these mutations have been functionally characterized, 6 the cellular signaling involved and gene targets are largely unknown. Defects in CcO originating from aberrations in nucleus-coded subunits are reported in several pathologic conditions; 7 however, their role in cancer development has not been investigated.…”