ORAI channels and cancer

Chalmers, Silke B.; Monteith, Gregory R.

doi:10.1016/j.ceca.2018.07.011

Cited by 55 publications

(58 citation statements)

References 85 publications

(147 reference statements)

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“…SOCE is the most ubiquitous pathway for Ca 2+ transport from the extracellular space and activated following the depletion of Ca 2+ stores from the ER. Recently, SOCE has emerged as critical machinery for Ca 2+ influx, contributing to various malignant phenotypes in cancer cells [44][45][46]. SOCE is also shown to be responsible for cisplatin-induced apoptosis [20].…”

Section: Strikingly Dats Seems To Evoke Ca 2+mentioning

confidence: 99%

The Mitochondrial Ca2+ Overload via Voltage-Gated Ca2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide

Nakagawa

Suzuki-Karasaki²,

Suzuki‐Karasaki³

et al. 2020

IJMS

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Allium vegetables such as garlic (Allium sativum L.) are rich in organosulfur compounds that prevent human chronic diseases, including cancer. Of these, diallyl trisulfide (DATS) exhibits anticancer effects against a variety of tumors, including malignant melanoma. Although previous studies have shown that DATS increases intracellular calcium (Ca2+) in different cancer cell types, the role of Ca2+ in the anticancer effect is obscure. In the present study, we investigated the Ca2+ pathways involved in the anti-melanoma effect. We used melittin, the bee venom that can activate a store-operated Ca2+ entry (SOCE) and apoptosis, as a reference. DATS increased apoptosis in human melanoma cell lines in a Ca2+-dependent manner. It also induced mitochondrial Ca2+ (Ca2+mit) overload through intracellular and extracellular Ca2+ fluxes independently of SOCE. Strikingly, acidification augmented Ca2+mit overload, and Ca2+ channel blockers reduced the effect more significantly under acidic pH conditions. On the contrary, acidification mitigated SOCE and Ca2+mit overload caused by melittin. Finally, Ca2+ channel blockers entirely inhibited the anti-melanoma effect of DATS. Our findings suggest that DATS explicitly evokes Ca2+mit overload via a non-SOCE, thereby displaying the anti-melanoma effect.

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Section: Strikingly Dats Seems To Evoke Ca 2+mentioning

confidence: 99%

The Mitochondrial Ca2+ Overload via Voltage-Gated Ca2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide

Nakagawa

Suzuki-Karasaki²,

Suzuki‐Karasaki³

et al. 2020

IJMS

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“…This contrasts, however, with the ubiquitous expression of ORAI and STIM genes in many other tissues and the presence of SOCE in many cell types in humans, mice and other species. Furthermore, studies of mice with genetic deletion of Orai and Stim genes have revealed additional roles of CRAC channels in health and disease that go beyond the phenotype of patients with CRAC channelopathy and that are the topic of a second group of reviews in this special issue [20][21][22][23][24][25]. Arguably the most dramatic difference between CRAC channel deficient patients and mice is that Orai1 -/or Stim1 -/mice are not viable, which is most apparent on the inbred C57BL/6 background.…”

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confidence: 99%

“…Over the last 10 years, many labs have investigated the role of SOCE in cancer growth, proliferation and metastasis. Chalmers & Monteith review the current literature on Ca 2+ signals in cancer and how they control the properties of cancer cells including their proliferation, invasion and resistance to cell death [20]. Whereas much earlier work on Ca 2+ signaling in cancer had focused on transient receptor potential (TRP) channels, the discovery of ORAI and STIM genes has attracted considerable interest in SOCE as a pathway deregulated in tumor cells.…”

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confidence: 99%

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CRAC channels and disease – From human CRAC channelopathies and animal models to novel drugs

Feske

2019

Cell Calcium

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Ca 2+ release-activated Ca 2+ (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca 2+ entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders. CRAC channels mediate Ca 2+ influx in many cell types. They are traditionally viewed as being especially important for the function of electrically non-excitable cells including, but not limited to, immune cells. Ca 2+ influx mediated by CRAC channels is called storeoperated Ca 2+ entry, or SOCE, because it is regulated by the filling state of intracellular (mainly ER) Ca 2+ stores [1]. The engagement of cell surface receptors including G protein coupled receptors (GPCR) and immunoreceptors such as T cell, B cell and Fc receptors results in the production of inositol-1,4,5-trisphosphate (IP 3) that binds to the IP 3 receptor (IP 3 R) located in the membrane of the ER, which is a Ca 2+ permeable ion channel and mediates the release of Ca 2+ from the ER. This release has two consequences: an increase in the cytoplasmic Ca 2+ concentration and a decrease in the Ca 2+ concentration of the ER. The latter results in the dissociation of Ca 2+ in the ER from STIM proteins, conformational changes of STIM1 and STIM2 and their translocation to ER-plasma membrane junctions. In these junctions, STIM proteins cluster and recruit ORAI proteins to form microdomains of localized Ca 2+ influx. ORAI1, and its closely related homologues ORAI2 and ORAI3, is a Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Competing Interests. S.F. is a scientific cofounder of Calcimedica.

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“…Thus, its cellular level is always subjected to tight regulations, mainly by the activity of three plasma membrane Ca 2+ channels, voltage-gated Ca 2+ channels, Orai-mediated store-operated channels, and transient receptor potential-mediated Ca 2+ channels. It has been revealed that disruption in the expression or function of these channels is often correlated with carcinogenesis and/or chemoresistance [119,120]. Hence, targeting their expression level or function may serve as an effective strategy to improve cancer treatment.…”

Section: Ca 2+ Channelsmentioning

confidence: 99%

Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance

Almasi

Hiani

2020

Cancers

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Improving the therapeutic efficacy of conventional anticancer drugs represents the best hope for cancer treatment. However, the shortage of druggable targets and the increasing development of anticancer drug resistance remain significant problems. Recently, membrane transport proteins have emerged as novel therapeutic targets for cancer treatment. These proteins are essential for a plethora of cell functions ranging from cell homeostasis to clinical drug toxicity. Furthermore, their association with carcinogenesis and chemoresistance has opened new vistas for pharmacology-based cancer research. This review provides a comprehensive update of our current knowledge on the functional expression profile of membrane transport proteins in cancer and chemoresistant tumours that may form the basis for new cancer treatment strategies.

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ORAI channels and cancer

Cited by 55 publications

References 85 publications

The Mitochondrial Ca2+ Overload via Voltage-Gated Ca2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide

The Mitochondrial Ca2+ Overload via Voltage-Gated Ca2+ Entry Contributes to an Anti-Melanoma Effect of Diallyl Trisulfide

CRAC channels and disease – From human CRAC channelopathies and animal models to novel drugs

Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance

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