Effect of TRPM2-Mediated Calcium Signaling on Cell Proliferation and Apoptosis in Esophageal Squamous Cell Carcinoma

Wang, Xingbang; Xiao, Yong; Huang, Mingming; Shen, Bing; Xue, Haowei; Wu, Kaile

doi:10.1177/15330338211045213

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…4 ). TRPM2 channel protein expression level has been found to be increased in esophageal squamous cell carcinoma tumor tissue compared with adjacent normal tissue 15 . TRPM2 participated in the ROS hydrogen peroxide-induced increase in intracellular calcium, which inhibited cell proliferation and enhanced apoptosis.…”

Section: Resultsmentioning

confidence: 99%

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Pan-cancer analyses reveal the genetic and pharmacogenomic landscape of transient receptor potential channels

Pan

Gao

et al. 2022

npj Genom. Med.

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Transient-receptor potential (TRP) channels comprise a diverse family of ion channels, which play important roles in regulation of intracellular calcium. Emerging evidence has revealed the critical roles of TRP channels in tumor development and progression. However, we still lack knowledge about the genetic and pharmacogenomics landscape of TRP genes across cancer types. Here, we comprehensively characterized the genetic and transcriptome alterations of TRP genes across >10,000 patients of 33 cancer types. We revealed prevalent somatic mutations and copy number variation in TRP genes. In particular, mutations located in transmembrane regions of TRP genes were likely to be deleterious mutations (p-values < 0.001). Genetic alterations were correlated with transcriptome dysregulation of TRP genes, and we found that TRPM2, TRPM8, and TPRA1 showed extent dysregulation in cancer. Patients with TRP gene alterations were with significantly higher hypoxia scores, tumor mutation burdens, tumor stages and grades, and poor survival. The alterations of TRP genes were significantly associated with the activity of cancer-related pathways. Moreover, we found that the expression of TRP genes were potentially useful for development of targeted therapies. Our study provided the landscape of genomic and transcriptomic alterations of TPRs across 33 cancer types, which is a comprehensive resource for guiding both mechanistic and therapeutic analyses of the roles of TRP genes in cancer. Identifying the TRP genes with extensive genetic alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.

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Section: Resultsmentioning

confidence: 99%

“…9 ). TRPM2 has been demonstrated to be participated in the ROS hydrogen peroxide-induced increase in intracellular calcium 15 . It has been shown that inhibiting the TRPA1 ion channels are critical for breaking down the oxidative stress defense system and overcome cellular resistance 24 .…”

Section: Resultsmentioning

confidence: 99%

Pan-cancer analyses reveal the genetic and pharmacogenomic landscape of transient receptor potential channels

Pan

Gao

et al. 2022

npj Genom. Med.

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“…LYZ-81, an inhibitor of ORP4L, is designed to selectively eradicate LCSs in vitro and in vivo ( 43 ). TRPM2 is a Ca 2+ -operable, nonselective cation channel in response to reactive oxygen species (ROS) ( 44 ). High TRPM2 expression is positively correlated with AML proliferation and survival advantage through modulation of mitochondrial function, ROS production, and autophagy ( 45 ).…”

Section: Mitochondrial Metabolic Reprogramming In Amlmentioning

confidence: 99%

Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia

Feng,

Zhang,

Gao

et al. 2023

Front. Oncol.

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Chemoresistance often complicates the management of cancer, as noted in the instance of acute myeloid leukemia (AML). Mitochondrial function is considered important for the viability of AML blasts and appears to also modulate chemoresistance. As mitochondrial metabolism is aberrant in AML, any distinct pathways could be directly targeted to impact both cell viability and chemoresistance. Therefore, identifying and targeting those precise rogue elements of mitochondrial metabolism could be a valid therapeutic strategy in leukemia. Here, we review the evidence for abnormalities in mitochondria metabolic processes in AML cells, that likely impact chemoresistance. We further address several therapeutic approaches targeting isocitrate dehydrogenase 2 (IDH2), CD39, nicotinamide phosphoribosyl transferase (NAMPT), electron transport chain (ETC) complex in AML and also consider the roles of mesenchymal stromal cells. We propose the term “mitotherapy” to collectively refer to such regimens that attempt to override mitochondria-mediated metabolic reprogramming, as used by cancer cells. Mounting evidence suggests that mitotherapy could provide a complementary strategy to overcome chemoresistance in liquid cancers, as well as in solid tumors.

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“…An increase in the [Ca 2+ ]i has been known to be one of the main causes of cell death in various cell types [40]. In fact, earlier research has provided evidence to support one of the main functions of the TRPM2 channel in facilitating the influx of the extracellular Ca 2+ , leading to an increase in the [Ca 2+ ]i, which ultimately drives cell death [41,42]. To investigate the role of the TRPM2 channel in HT22 cell responses to Cu, we investigated whether Cu induces the TRPM2 channel activation by measuring the increase in the [Ca 2+ ]i in HT22 cells after exposure to Cu, using single-cell calcium imaging.…”

Section: Expression Of Trpm2 and Cu-induced Increase In The [Ca 2+ ]Imentioning

confidence: 99%

Signalling Mechanism in TRPM2-dependent Copper- induced HT22 Cell Death

Rathakrishnan,

Hazanol,

Dali

et al. 2023

J Biochem Microbiol Biotechnol

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Copper (Cu) is one of the critical elements needed by the human body. However, this metal can cause cytotoxicity when present in excess amounts. In this study, we used HT22 hippocampus cells to examine the function of the Ca2+-permeable transient receptor melastatin 2 (TRPM2) channel in Cu-induced neuronal cell death and the underlying mechanisms. Immunocytochemistry, single-cell imaging, acridine orange/propidium iodide (AO/PI) cell death assay and immunofluorescence microscopy were applied to interpret the mechanisms involved in Cu-induced HT22 cell death. Treatment of 30-300 μM Cu induced an increase in the [Ca2+]i in HT22 cells. Further analysis indicates that Cu exposure induced substantial HT22 cell death. Such response on HT22 cells was significantly inhibited by 2-aminoethoxydiphenyl borate (2-APB) and N-(p-amylcinnamoyl)anthranilic acid (ACA), TRPM2 channel inhibitors. Furthermore, Cu-induced HT22 cell death was suppressed by pharmacologically inhibiting poly(ADPR) polymerase (PARP) using PJ-34 and DPQ. It is known that the activation of TRPM2 channel is via the increase of intracellular reactive oxygen species (ROS). A significant concentration-dependent increase in the generation of ROS was observed in HT22 following the treatment with 30-300 μM Cu. Additionally, Cu-induced HT22 cell death was ablated by inhibiting PKC using CTC, a PKC inhibitor and NADPH oxidase (NOX) using DPI, a NOX generic inhibitor and GKT137831, a NOX1/4-specific inhibitor. Overall, our present study provides evidence suggesting that PKC/NOX/ROS/PARP is an important signalling pathway in Cu-induced activation of the TRPM2 channel and increase in the [Ca2+]i which eventually results in the toxicity of HT22 cells. These results provide new insights into the mechanisms of neurological-associated Cu-induced diseases.

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Effect of TRPM2-Mediated Calcium Signaling on Cell Proliferation and Apoptosis in Esophageal Squamous Cell Carcinoma

Cited by 11 publications

References 30 publications

Pan-cancer analyses reveal the genetic and pharmacogenomic landscape of transient receptor potential channels

Pan-cancer analyses reveal the genetic and pharmacogenomic landscape of transient receptor potential channels

Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia

Signalling Mechanism in TRPM2-dependent Copper- induced HT22 Cell Death

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