Mitochondria and the permeability transition pore in cancer metabolic reprogramming

Guo, Lishu

doi:10.1016/j.bcp.2021.114537

Cited by 13 publications

(17 citation statements)

References 185 publications

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“…Metabolic switch is a hallmark of cancer, allowing cancer cells to adapt to microenvironment change [ 5 , 6 ]. Glycolytic metabolism is a main source of ATP provision for cancer cells, and glycolysis provides metabolites and acidic microenvironment that favors malignant development of tumor [ 7 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is urgent and significant to develop new therapeutic targets and strategies to fight against cancer. Metabolic plasticity allows tumor cells to reprogram metabolism pathway to cope with tumor microenvironment, which is a hallmark of cancer [ 5 ]. Cancer cells undergo enhanced glycolysis even in presence of oxygen, and this phenomenon was named ‘Warburg effect’ [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2)

Deng

Jiang

et al. 2021

Bioengineered

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Gastric cancer is one of the most common malignancy with a leading mortality rate worldwide. Despite the progress in the diagnosis and therapeutic strategy, the associated mortality is still growing. It is of great significance to understand molecular mechanisms of the development of gastric cancer. Glycolysis is a main source of ATP provision for cancer cells including gastric cancer, and targeting glycolysis is a promising therapeutic strategy. Centromere protein U (CENPU) has been found to be overexpressed in many types of cancer. Downregulation of CENPU suppresses the proliferation and invasion of cancer cells. High mobility group box 2 (HMGB2) is identified as a biomarker to diagnose of gastric cancer. Knockdown of HMGB2 inhibits proliferation and glycolysis in gastric cancer cells. In this work, we identified that CENPU was upregulated in gastric cancer. Knockdown of CENPU was able to suppress the proliferation and glycolysis of gastric cancer cells. Further the results showed that the anti-cancer effect of CENPU was HMGB2-dependent. Taken together, CENPU is an upstream factor of HMGB2, which regulates proliferation and glycolysis of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2)

Deng

Jiang

et al. 2021

Bioengineered

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“…In the current study, we examined the transcript levels of various components of the Ca 2+ toolkit in OAC samples and in normal oesophageal samples, using data from both The Cancer Genome Atlas (TCGA) and the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium [79,80]. We focused on a gene list of Ca 2+ -toolkit components, updated from an original review of these [13], with the addition of known components involved in acid-sensing [10] and those related to mitochondrial function [19,20,[22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Alterations in the Ca2+ toolkit in oesophageal adenocarcinoma

Cutliffe

McKenna

Chandrashekar

et al. 2021

Exploration of Targeted Anti-Tumor Therapy

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Aim: To investigate alterations in transcription of genes, encoding Ca2+ toolkit proteins, in oesophageal adenocarcinoma (OAC) and to assess associations between gene expression, tumor grade, nodal-metastatic stage, and patient survival. Methods: The expression of 275 transcripts, encoding components of the Ca2+ toolkit, was analyzed in two OAC datasets: the Cancer Genome Atlas [via the University of Alabama Cancer (UALCAN) portal] and the oesophageal-cancer, clinical, and molecular stratification [Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS)] dataset. Effects of differential expression of these genes on patient survival were determined using Kaplan-Meier log-rank tests. OAC grade- and metastatic-stage status was investigated for a subset of genes. Adjustment for the multiplicity of testing was made throughout. Results: Of the 275 Ca2+-toolkit genes analyzed, 75 displayed consistent changes in expression between OAC and normal tissue in both datasets. The channel-encoding genes, N-methyl-D-aspartate receptor 2D (GRIN2D), transient receptor potential (TRP) ion channel classical or canonical 4 (TRPC4), and TRP ion channel melastatin 2 (TRPM2) demonstrated the greatest increase in expression in OAC in both datasets. Nine genes were consistently upregulated in both datasets and were also associated with improved survival outcomes. The 6 top-ranking genes for the weighted significance of altered expression and survival outcomes were selected for further analysis: voltage-gated Ca2+ channel subunit α 1D (CACNA1D), voltage-gated Ca2+ channel auxiliary subunit α2 δ4 (CACNA2D4), junctophilin 1 (JPH1), acid-sensing ion channel 4 (ACCN4), TRPM5, and secretory pathway Ca2+ ATPase 2 (ATP2C2). CACNA1D, JPH1, and ATP2C2 were also upregulated in advanced OAC tumor grades and nodal-metastatic stages in both datasets. Conclusions: This study has unveiled alterations of the Ca2+ toolkit in OAC, compared to normal tissue. Such Ca2+ signalling findings are consistent with those from studies on other cancers. Genes that were consistently upregulated in both datasets might represent useful markers for patient diagnosis. Genes that were consistently upregulated, and which were associated with improved survival, might be useful markers for patient outcome. These survival-associated genes may also represent targets for the development of novel chemotherapeutic agents.

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“…Mitochondrial calcium overload and oxidative stress may trigger opening of the mitochondrial permeability transition pore (PTP), resulting in the rupture of outer mitochondrial membrane and the depletion of ATP, eventually apoptotic and necrotic cell death ( 1 ). Cyclophilin D (CyPD), encoded by PPIF (peptidylprolyl isomerase F) gene, is a most well-characterized regulator of PTP.…”

mentioning

confidence: 99%

“…IF1 overexpression in colon cancer results in generation of reactive oxygen species (ROS), which triggers a prosurvival and proliferative response ( 26 ). The relative expression level of IF1 varies between different tissues and cell types ( 25 ), which may contribute to heterogeneous phenotypes of tumors in metabolic phenotypes and chemoresistance ( 1 , 28 ).…”

mentioning

confidence: 99%

Mitochondria and the permeability transition pore in cancer metabolic reprogramming

Cited by 13 publications

References 185 publications

Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2)

Centromere protein U (CENPU) promotes gastric cancer cell proliferation and glycolysis by regulating high mobility group box 2 (HMGB2)

Alterations in the Ca2+ toolkit in oesophageal adenocarcinoma

Mitochondrial ATP synthase inhibitory factor 1 interacts with the p53–cyclophilin D complex and promotes opening of the permeability transition pore

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