Calcium signaling in cancer progression and therapy

Wu, Ling; Lian, Weidong; Zhao, Liang

doi:10.1111/febs.16133

Cited by 46 publications

(43 citation statements)

References 216 publications

(250 reference statements)

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“…Changes in intracellular Ca 2+ concentration are affected by the influx of extracellular Ca 2+ and the release of ca 2+ from intracellular ca 2+ stores, such as the ER, mitochondria and lysosomes. When cells are excited by external stimuli, various Ca 2+ channels are opened or closed, which results in the dysregulation of ca 2+ homeostasis (22,23). Previous studies have reported that the Ca 2+ signaling pathway is a key regulator of nutrient uptake, metabolism and utilization (24,25).…”

Section: Physiological Role Of Ca 2+ In the Livermentioning

confidence: 99%

Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

et al. 2022

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Non-alcoholic fatty liver disease (NAFLd) is a clinically progressive illness that can advance from simple fatty liver to non-alcoholic hepatitis and liver fibrosis. Cirrhosis and hepatocellular carcinoma are two of the most common diseases caused by NAFLD. As there are no early disease biomarkers and no US Food and drug Administration-approved medications, treatment for NAFLd is still focused on altering lifestyle and dietary habits, which makes it difficult to treat effectively. As a result, a novel treatment is urgently needed to prevent NAFLD progression. Calcium (Ca 2+ ) channels regulate intracellular ca 2+ homeostasis via the mediation of ca 2+ flow. Previous studies have reported that Ca 2+ channel expression varies throughout the development and progression of NAFLd, which results in the dysregulation of intracellular ca 2+ homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction and autophagy suppression, all of which contribute to NAFLD progression. Several types of ca 2+ channels (including two-pore segment channel 2, transient receptor potential, inositol triphosphate receptor, voltage-dependent anion channel 1, store-operated ca 2+ entry, purinergic receptor X7 and potassium ca 2+ -activated channel subfamily N member 4) have been identified as potential targets for preventing NAFLd development and controlling intracellular ca 2+ homeostasis. To achieve this, these channels can be blocked or activated, which exerts anti-steatotic, anti-inflammatory, anti-fibrotic and other effects, which ultimately prevents the development of NAFLD. In the present review NAFLd therapeutics and the treatments that target ca 2+ channels that are currently being developed were examined. Contents 1. Introduction 2. Physiological role of Ca 2+ in the liver 3. Dysregulation of Ca 2+ channel expression and the disturbance of Ca 2+ homeostasis in NAFLd 4. Ca 2+ channels in the development and progression of NAFLd and as an NAFLd therapeutic target 5. Conclusion and future perspectives

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Section: Physiological Role Of Ca 2+ In the Livermentioning

confidence: 99%

Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

et al. 2022

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“…However, cellular Ca 2+ signaling proteomes, such as Ca 2+ channels, and Ca 2+ -binding proteins including calmodulin (CaM) and Ca 2+ -sensing receptor (CaSR), are tissue-specific and produce distinct Ca 2+ signals suitable for tissue physiology [ 13 ]. Cytosolic Ca 2+ signals practically participate in every aspect of cellular life, and rigorous regulation of Ca 2+ homeostasis is important for preventing dysfunctions that lead to pathological changes [ 14 ]. In a pathological environment, remodeling of Ca 2+ flux contributes to processes important for cancer progressions, such as uncontrolled proliferation, invasiveness of tumor cells, and the development of resistance to cancer therapies [ 15 ].…”

Section: Ca 2+mentioning

confidence: 99%

Roles of calcium signaling in cancer metastasis to bone

Xie

Chen

Jiang

et al. 2022

Exploration of Targeted Anti-Tumor Therapy

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Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hypercalcemia, pathologic fractures, spinal cord compression, and even death. However, the underlying mechanisms of bone metastasis were not clear. The role of calcium (Ca2+) in cancer cell proliferation, migration, and invasion has been well established. Interestingly, emerging evidence indicates that Ca2+ signaling played a key role in bone metastasis, for it not only promotes cancer progression but also mediates osteoclasts and osteoblasts differentiation. Therefore, Ca2+ signaling has emerged as a novel therapeutical target for cancer bone metastasis treatments. Here, the role of Ca2+ channels and Ca2+-binding proteins including calmodulin and Ca2+-sensing receptor in bone metastasis, and the perspective of anti-cancer bone metastasis therapeutics via targeting the Ca2+ signaling pathway are summarized.

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“…Ion channels are versatile regulators of several physiological and pathophysiological mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. The calcium signaling pathway, the fourth enriched pathway in JIMT-1 cells, can precisely regulate many master regulators in cancer via the opening of plasmalemmal calcium channels in response to various stimuli leading to localized high levels of Ca2+, which subsequently influences gene expression (Wu et al, 2021). Ion channels are the key regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein-protein interactions being one of their main regulatory mechanisms.…”

Section: Integration Of Dna Methylation and Gene Expression Datamentioning

confidence: 99%

Decitabine-induced DNA methylation-mediated transcriptomic reprogramming in human breast cancer cell lines; the impact of DCK overexpression

Buociková

Tyciakova

Pilalis³

et al. 2022

Front. Pharmacol.

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Decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, is tested in combination with conventional anticancer drugs as a treatment option for various solid tumors. Although epigenome modulation provides a promising avenue in treating resistant cancer types, more studies are required to evaluate its safety and ability to normalize the aberrant transcriptional profiles. As deoxycytidine kinase (DCK)-mediated phosphorylation is a rate-limiting step in DAC metabolic activation, we hypothesized that its intracellular overexpression could potentiate DAC’s effect on cell methylome and thus increase its therapeutic efficacy. Therefore, two breast cancer cell lines, JIMT-1 and T-47D, differing in their molecular characteristics, were transfected with a DCK expression vector and exposed to low-dose DAC (approximately IC20). Although transfection resulted in a significant DCK expression increase, further enhanced by DAC exposure, no transfection-induced changes were found at the global DNA methylation level or in cell viability. In parallel, an integrative approach was applied to decipher DAC-induced, methylation-mediated, transcriptomic reprogramming. Besides large-scale hypomethylation, accompanied by up-regulation of gene expression across the entire genome, DAC also induced hypermethylation and down-regulation of numerous genes in both cell lines. Interestingly, TET1 and TET2 expression halved in JIMT-1 cells after DAC exposure, while DNMTs’ changes were not significant. The protein digestion and absorption pathway, containing numerous collagen and solute carrier genes, ranking second among membrane transport proteins, was the top enriched pathway in both cell lines when hypomethylated and up-regulated genes were considered. Moreover, the calcium signaling pathway, playing a significant role in drug resistance, was among the top enriched in JIMT-1 cells. Although low-dose DAC demonstrated its ability to normalize the expression of tumor suppressors, several oncogenes were also up-regulated, a finding, that supports previously raised concerns regarding its broad reprogramming potential. Importantly, our research provides evidence about the involvement of active demethylation in DAC-mediated transcriptional reprogramming.

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Calcium signaling in cancer progression and therapy

Cited by 46 publications

References 216 publications

Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Roles of calcium signaling in cancer metastasis to bone

Decitabine-induced DNA methylation-mediated transcriptomic reprogramming in human breast cancer cell lines; the impact of DCK overexpression

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Calcium signaling in cancer progression and therapy

Cited by 46 publications

References 216 publications

Role of Ca2+ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Role of Ca2+ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Roles of calcium signaling in cancer metastasis to bone

Decitabine-induced DNA methylation-mediated transcriptomic reprogramming in human breast cancer cell lines; the impact of DCK overexpression

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Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)

Role of Ca²⁺ channels in non-alcoholic fatty liver disease and their implications for therapeutic strategies (Review)