Involvement of increased p53 expression in the decrease of mitochondrial DNA copy number and increase of SUVmax of FDG-PET scan in esophageal squamous cell carcinoma

Lin, Cheng‐Chieh; Huang, Yu‐Chen; Pan, Siao-Cian; Cheng, Chih‐Tao; Liu, Chia‐Chuan; Shih, Chun-Che; Ho, Hsiang‐Ling; Yeh, Yi‐Chen; Chou, Teh-Ying; Lee, Ming-Yuan; Wei, Yau‐Huei

doi:10.1016/j.mito.2019.05.001

Cited by 7 publications

(7 citation statements)

References 67 publications

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“…In addition, it was reported that during reprogramming there was not only a reduction of mitochondrial mass, but also in mitochondrial DNA (mtDNA) [21]. Consistent with the comparable increase in mitochondrial mass, we observed a sharp increase in mtDNA (Figure S1D,F), especially after one day of treatment with 1500 µM of melatonin in Cal-27 cells (Figure S1D).…”

Section: Melatonin Treatment Modifies the Mitochondrial Morphology Of Hnscc Cellssupporting

confidence: 88%

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Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function

et al. 2021

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Metabolic reprogramming, which is characteristic of cancer cells that rapidly adapt to the hypoxic microenvironment and is crucial for tumor growth and metastasis, is recognized as one of the major mechanisms underlying therapeutic resistance. Mitochondria, which are directly involved in metabolic reprogramming, are used to design novel mitochondria-targeted anticancer agents. Despite being targeted by melatonin, the functional role of mitochondria in melatonin’s oncostatic activity remains unclear. In this study, we aim to investigate the role of melatonin in mitochondrial metabolism and its functional consequences in head and neck cancer. We analyzed the effects of melatonin on head and neck squamous cell carcinoma (HNSCC) cell lines (Cal-27 and SCC-9), which were treated with 100, 500, and 1500 µM of melatonin for 1, 3, and 5 days, and found a connection between a change of metabolism following melatonin treatment and its effects on mitochondria. Our results demonstrate that melatonin induces a shift to an aerobic mitochondrial metabolism that is associated with changes in mitochondrial morphology, function, fusion, and fission in HNSCC. We found that melatonin increases oxidative phosphorylation (OXPHOS) and inhibits glycolysis in HNSCC, resulting in increased ROS production, apoptosis, and mitophagy, and decreased cell proliferation. Our findings highlight new molecular pathways involved in melatonin’s oncostatic activity, suggesting that it could act as an adjuvant agent in a potential therapy for cancer patients. We also found that high doses of melatonin, such as those used in this study for its cytotoxic impact on HNSCC cells, might lead to additional effects through melatonin receptors.

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Section: Melatonin Treatment Modifies the Mitochondrial Morphology Of Hnscc Cellssupporting

confidence: 88%

“…In addition, it was reported that during reprogramming there was not only a reduction of mitochondrial mass, but also in mitochondrial DNA (mtDNA) [21]. Consistent (in black and grey).…”

Section: Melatonin Treatment Modifies the Mitochondrial Morphology Of Hnscc Cellsmentioning

confidence: 84%

Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function

et al. 2021

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“…The decreased chromosomal aberrations were associated with the loss of hMLH1 or hMSH2 protein expressions, while p53 overexpression was not proven [54]. MMR and p53 were able to cooperate in modulating the sensitivity of the MMR-defective CRC cell line to cisplatin [55] (Table 1). Although only a few shorter telomeres are needed to trigger DDR, they form endassociations, leading to a DNA damage signal resulting in replicative senescence (cellular growth arrest, also called the M1 stage).…”

Section: Dna Damage Dna Repair and Tp53mentioning

confidence: 99%

“…The study by Lin et al on mitochondrial DNA (mtDNA) copy number represents an interesting attempt to investigate extragenomic DNA status to understand the biology and the progression of cancer, including its therapy [55]. Recent findings have illustrated that cancer cells with dysfunctional mtDNA (using cells devoid of mtDNA, 0 cells), when grafted in mice, acquire mtDNA from the host by "importing" whole mitochondria [127].…”

Section: The Interactions Of Dna Repair Telomere Homeostasis and P53 And The New Concept In Cancer Therapymentioning

confidence: 99%

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

Vodička

Anděra

Opattová

et al. 2021

Cancers

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The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and telomere shortening constitute the hallmarks of malignant diseases. DNA damage response (DDR) is a signaling network to process DNA damage with importance for both cancer development and chemotherapy outcome. DDR represents the complex events that detect DNA lesions and activate signaling networks (cell cycle checkpoint induction, DNA repair, and induction of cell death). TP53, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of TP53 has an impact on DDR, and somatic mutations in this gene represent one of the critical events in human carcinogenesis. Telomere dysfunction in cells that lack p53-mediated surveillance of genomic integrity along with the involvement of DNA repair in telomeric DNA regions leads to genomic instability. While the role of individual players (DDR, telomere homeostasis, and TP53) in human cancers has attracted attention for some time, there is insufficient understanding of the interactions between these pathways. Since solid cancer is a complex and multifactorial disease with considerable inter- and intra-tumor heterogeneity, we mainly dedicated this review to the interactions of DNA repair, telomere homeostasis, and TP53 mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy.

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“…In this study, we constructed 2 ESCC-related co-expression modules from 2 GEO datasets. Functional enrichment analysis results demonstrated that genes in the 2 co-expression modules were significantly involved in ESCC-related pathways such as mitochondrial gene expression (17), ncRNA metabolic process (19), and chromosome segregation (20), which confirmed the clinical significance of the 2 modules for ESCC. Based on univariate and multivariate Cox regression analyses, an 8-gene model was built for ESCC.…”

Section: Discussionmentioning

confidence: 61%

Development of a prognostic nomogram based on an eight-gene signature for esophageal squamous cell carcinoma by weighted gene co-expression network analysis (WGCNA)

Xie¹,

Yang²,

Wei³

et al. 2022

Ann Transl Med

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Background: Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignant tumor. This study aims to develop a robust prognostic model for ESCC. Methods: Expression profiles of ESCC were downloaded from the Gene Expression Omnibus (GEO) andThe Cancer Genome Atlas (TCGA) databases. Co-expressed modules were constructed by weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) between ESCC and normal samples were identified with the screening criteria of adjusted P value <0.05 and log |fold change (FC)| >1. After univariate and multivariate Cox regression analysis, an 8-gene module was constructed. A receiver operating characteristic (ROC) curve for overall survival (OS) was used to assess the prediction efficacy of the risk score. A nomogram was developed based on the risk score, age, gender, and stage for 1-, 2and 3-year survival. The potential biological functions and pathways of the 8 genes were predicted using the Metascape database. Results:The 2 ESCC-related co-expression modules were built via WGCNA. Among all DEGs, 55 survival-related genes were identified for ESCC. Based on these genes, an 8-gene module was constructed, composed of CFAP53, FCGR2A, FCGR3A, GNGT1, IGF2, LINC01524, MAGEA3, and MAGEA6. The area under the curve (AUC) was 0.961, suggesting that the risk score could effectively predict the OS of patients with ESCC. Furthermore, the nomogram exhibited high accuracy in predicting the survival rate of ESCC patients at 1, 2, and 3 years. These genes were mainly involved in ESCC-related pathways such as extracellular matrix organization, collagen formation, and blood vessel development.Conclusions: Our nomogram based on the 8-gene risk score could be a reliable prognostic tool for ESCC.

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Involvement of increased p53 expression in the decrease of mitochondrial DNA copy number and increase of SUVmax of FDG-PET scan in esophageal squamous cell carcinoma

Cited by 7 publications

References 67 publications

Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function

Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

Development of a prognostic nomogram based on an eight-gene signature for esophageal squamous cell carcinoma by weighted gene co-expression network analysis (WGCNA)

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