The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

Adiga, Divya; Radhakrishnan, Raghu; Chakrabarty, Sanjiban; Kumar, Prashant; Kabekkodu, Shama Prasada

doi:10.1159/000512277

Cited by 14 publications

(13 citation statements)

References 309 publications

(242 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Calcium is the most universal second messenger, mediating signaling pathways that control cell cycle, gene expression, excitability, trafficking, secretion, and cell death [ 2 , 56 , 91 – 94 ]. Changes is free cytosolic Ca 2+ also facilitate cell motility, differentiation, and tumorigenesis [ 95 – 97 ]. In intracellular parasites, host cell invasion [ 4 , 48 , 98 ] and egress are also Ca 2+ dependent [ 54 , 99 – 103 ].…”

Section: Ion Channel Repertoiresmentioning

confidence: 99%

Down the membrane hole: Ion channels in protozoan parasites

Jiménez

Sebastian

2022

PLoS Pathog

View full text Add to dashboard Cite

Parasitic diseases caused by protozoans are highly prevalent around the world, disproportionally affecting developing countries, where coinfection with other microorganisms is common. Control and treatment of parasitic infections are constrained by the lack of specific and effective drugs, plus the rapid emergence of resistance. Ion channels are main drug targets for numerous diseases, but their potential against protozoan parasites is still untapped. Ion channels are membrane proteins expressed in all types of cells, allowing for the flow of ions between compartments, and regulating cellular functions such as membrane potential, excitability, volume, signaling, and death. Channels and transporters reside at the interface between parasites and their hosts, controlling nutrient uptake, viability, replication, and infectivity. To understand how ion channels control protozoan parasites fate and to evaluate their suitability for therapeutics, we must deepen our knowledge of their structure, function, and modulation. However, methodological approaches commonly used in mammalian cells have proven difficult to apply in protozoans. This review focuses on ion channels described in protozoan parasites of clinical relevance, mainly apicomplexans and trypanosomatids, highlighting proteins for which molecular and functional evidence has been correlated with their physiological functions.

show abstract

Section: Ion Channel Repertoiresmentioning

confidence: 99%

Down the membrane hole: Ion channels in protozoan parasites

Jiménez

Sebastian

2022

PLoS Pathog

View full text Add to dashboard Cite

show abstract

“…Ca 2+ , a ubiquitous second messenger, is critical to cancer development, including metastasis and therapy resistance [ 17 ]. Ca 2+ has been widely demonstrated to manipulate events critical to metastasis, including the EMT [ 112 ], invadosome formation, ECM degradation [ 113 ] and angiogenesis [ 114 ]. Serum Ca 2+ level is positively associated with the risk of node metastasis in endometrial and breast cancer [ 115 , 116 ], but low serum calcium level indicates poor distant metastasis-free survival of patients with nasopharyngeal carcinoma [ 117 ].…”

Section: Roles Of Calcium Signaling In Cancer Metastasismentioning

confidence: 99%

Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets

Cui

Zhang

Liu

et al. 2021

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

Metastasis is still the primary cause of cancer-related mortality. However, the underlying mechanisms of cancer metastasis are not yet fully understood. Currently, the epithelial-mesenchymal transition, metabolic remodeling, cancer cell intercommunication and the tumor microenvironment including diverse stromal cells, are reported to affect the metastatic process of cancer cells. Calcium ions (Ca2+) are ubiquitous second messengers that manipulate cancer metastasis by affecting signaling pathways. Diverse transporter/pump/channel-mediated Ca2+ currents form Ca2+ oscillations that can be decoded by Ca2+-binding proteins, which are promising prognostic biomarkers and therapeutic targets of cancer metastasis. This paper presents a review of the advances in research on the mechanisms underlying cancer metastasis and the roles of Ca2+-related signals in these events.

show abstract

“…It has also been shown that calcium regulates mitochondrial and cellular reactive oxygen species (ROS) levels, the latter mainly through the regulation of NADPH oxidases [ 13 ]. Besides its role in cell proliferation, calcium homeostasis is involved in epithelial-mesenchymal transition (EMT) [ 14 ]. EMT is involved in the formation of metastasis through losing the epithelial phenotype and increasing the expression of proteins that promote unstable junctions between epithelial cells such as N-cadherin [ 15 ], thereby being another important factor determining cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Calcium acts as a central player in melatonin antitumor activity in sarcoma cells

et al. 2022

View full text Add to dashboard Cite

Purpose Chondrosarcoma and osteosarcoma are the most frequently occurring bone cancers. Although surgery and chemotherapy are currently clinically applied, improved treatment options are urgently needed. Melatonin is known to inhibit cell proliferation in both tumor types. Although the underlying mechanisms are not clear yet, calcium homeostasis has been reported to be a key factor in cancer biology. Here, we set out to investigate whether regulation of calcium by this indolamine may be involved in its antitumor effect. Methods Cell viability was measured using a MTT assay and flow cytometry was used to measure levels of cytosolic calcium, intracellular oxidants, mitochondrial membrane potential and cell cycle progression. Mitochondrial calcium was analyzed by fluorimetry. Cell migration was determined using a scratch wound-healing assay. Western blot analysis was used to assess the expression of proteins related to cell cycle progression, epithelial to mesenchymal transition (EMT), Ac-CoA synthesis and intracellular signaling pathways. Results We found that melatonin decreases cytosolic and mitochondrial Ca2+ levels, intracellular oxidant levels, mitochondrial function and the expression of the E1 subunit of the pyruvate dehydrogenase complex. These changes were found to be accompanied by decreases in cell proliferation, cell migration and EMT marker expression. The addition of CaCl2 prevented the changes mentioned above, while co-treatment with the calcium chelator BAPTA enhanced the effects. Conclusions Our data indicate that regulation of calcium homeostasis is a key factor in the inhibition of cell proliferation and migration by melatonin. This effect should be taken into consideration in combined therapies with traditional or new antitumor compounds, since it may circumvent therapy resistance.

show abstract

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

Cited by 14 publications

References 309 publications

Down the membrane hole: Ion channels in protozoan parasites

Down the membrane hole: Ion channels in protozoan parasites

Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets

Calcium acts as a central player in melatonin antitumor activity in sarcoma cells

Contact Info

Product

Resources

About