Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma

Benzerdjeb, Nazim; Sevestre, Henri; Ahidouch, Ahmed; Ouadid-Ahidouch, Halima

doi:10.18632/oncotarget.13149

Cited by 36 publications

(31 citation statements)

References 37 publications

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“…The transcription of Orai3 is regulated by estrogen receptor, which may explain the differential expression of Orai3 in different subtypes of breast cancer (34). The overexpression of Orai3 has also been reported in lung adenocarcinoma (110). In a cohort of 200 lung cancer patients, Orai3 protein and mRNA expression was increased in tumor tissues than in matched normal tissues, and Orai3 overexpression independently correlated with overall survival and metastasis free survival (110).…”

Section: The Dysregulation Of Soce In Cancermentioning

confidence: 87%

“…The overexpression of Orai3 has also been reported in lung adenocarcinoma (110). In a cohort of 200 lung cancer patients, Orai3 protein and mRNA expression was increased in tumor tissues than in matched normal tissues, and Orai3 overexpression independently correlated with overall survival and metastasis free survival (110). …”

Section: The Dysregulation Of Soce In Cancermentioning

confidence: 87%

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The store-operated calcium channels in cancer metastasis from cell migration invasion to metastatic colonization

Yang

2018

Front Biosci

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Store-operated calcium entry (SOCE) is the predominant calcium entry mechanism in most cancer cells. SOCE is mediated by the endoplasmic reticulum calcium sensor STIMs (STIM1 and 2) and plasma membrane channel forming unit Orais (Orai 1–3). In recent years there is increasing evidence indicating that SOCE in cancer cells is dysregulated to promote cancer cell migration, invasion and metastasis. The overexpression of STIM and Orai proteins has been reported to correlate with the metastatic progression of various cancers. The hyperactive SOCE may promote metastatic dissemination and colonization by reorganizing the actin cytoskeleton, degrading the extracellular matrix and remodeling the tumor microenvironment. Here we discuss how these recent progresses provide novel insights to our understanding of tumor metastasis.

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Section: The Dysregulation Of Soce In Cancermentioning

confidence: 87%

Section: The Dysregulation Of Soce In Cancermentioning

confidence: 87%

The store-operated calcium channels in cancer metastasis from cell migration invasion to metastatic colonization

Yang

2018

Front Biosci

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“…association with high levels of ORAI3 with greater metastasis and poorer survival in patients with resectable lung adenocarcinoma [27], decreased time to recurrence and lower overall survival in gastric cancers with high ORAI1 and STIM1 expression [25], and a correlation of high STIM1 levels with tumour size and lymph node metastases in cervical cancer [40]. However, such associations between expression and survival could simply be correlative; ORAI channel and STIM isoform levels may be a marker for a subtype associated with a poorer clinical outcome without itself contributing to disease progression.…”

Section: Accepted Manuscriptmentioning

confidence: 96%

“…For example, ORAI1 levels are elevated in cancer of the liver [23], osesophagus [24], stomach [25] and in renal cancer [26]. ORAI3 is elevated in lung cancer [27,28]. In vitro studies have also provided clues to potential changes in expression in cancer, such as high levels of ORAI2 in an acute myeloid leukaemia cell line [29].…”

Section: Orai Isoforms and Stim1 And Stim2 Expression Changes Have Bementioning

confidence: 99%

ORAI channels and cancer

Chalmers

Monteith

2018

Cell Calcium

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Cancer is a major cause of death. The diversity of cancer types and the propensity of cancers to acquire resistance to therapies, including new molecularly targeted and immune-based therapies, drives the search for new ways to understand cancer progression. The remodelling of calcium (Ca) signalling and the role of the Ca signal in controlling key events in cancer cells such as proliferation, invasion and the acquisition of resistance to cell death pathways is well established. Most of the work defining such changes has focused on Ca permeable Transient Receptor Potential (TRP) Channels and some voltage gated Ca channels. However, the identification of ORAI channels, a little more than a decade ago, has added a new dimension to how a Ca influx pathway can be remodelled in some cancers and also how calcium signalling could contribute to tumour progression. ORAI Ca channels are now an exemplar for how changes in the expression of specific isoforms of a Ca channel component can occur in cancer, and how such changes can vary between cancer types (e.g. breast cancer versus prostate cancer), and even subtypes (e.g. oestrogen receptor positive versus oestrogen receptor negative breast cancers). ORAI channels and store operated Ca entry are also highlighting the diverse roles of Ca influx pathways in events such as the growth and metastasis of cancers, the development of therapeutic resistance and the contribution of tumour microenvironmental factors in cancer progression. In this review we will highlight some of the studies that have provided evidence for the need to deepen our understanding of ORAI Ca channels in cancer. Many of these studies have also suggested new ways on how we can exploit the role of ORAI channels in cancer relevant processes to develop or inform new therapeutic strategies.

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“…Finally, Orai3 has also been reported to form ER Ca 2+ leakage channels [34]. Many pathophysiological cellular functions in aging and cancer involve SOCE and Orai3 [26,27,[35][36][37][38][39][40], highlighting the importance of understanding the pharmacology of Orai1/Orai3 heteromeric SOCE channels.…”

Section: Introductionmentioning

confidence: 99%

The Number and Position of Orai3 Units within Heteromeric Store-Operated Ca2+ Channels Alter the Pharmacology of ICRAC

Kappel

Kilch²,

Baur

et al. 2020

IJMS

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Store-operated heteromeric Orai1/Orai3 channels have been discussed in the context of aging, cancer, and immune cell differentiation. In contrast to homomeric Orai1 channels, they exhibit a different pharmacology upon application of reactive oxygen species (ROS) or 2-aminoethoxydiphenyl borate (2-APB) in various cell types. In endogenous cells, subunit composition and arrangement may vary and cannot be defined precisely. In this study, we used patch-clamp electrophysiology to investigate the 2-APB profile of store-operated and store-independent homomeric Orai1 and heteromeric Orai1/Orai3 concatenated channels with defined subunit compositions. As has been shown previous, one or more Orai3 subunit(s) within the channel result(s) in decreased Ca2+ release activated Ca2+ current (ICRAC). Upon application of 50 µM 2-APB, channels with two or more Orai3 subunits exhibit large outward currents and can be activated by 2-APB independent from storedepletion and/or the presence of STIM1. The number and position of Orai3 subunits within the heteromeric store-operated channel change ion conductivity of 2-APB-activated outward current. Compared to homomeric Orai1 channels, one Orai3 subunit within the channel does not alter 2-APB pharmacology. None of the concatenated channel constructs were able to exactly simulate the complex 2-APB pharmacology observed in prostate cancer cells. However, 2-APB profiles of prostate cancer cells are similar to those of concatenated channels with Orai3 subunit(s). Considering the presented and previous results, this indicates that distinct subtypes of heteromeric SOCE channels may be selectively activated or blocked. In the future, targeting distinct heteromeric SOCE channel subtypes may be the key to tailored SOCE-based therapies.

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Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma

Cited by 36 publications

References 37 publications

The store-operated calcium channels in cancer metastasis from cell migration invasion to metastatic colonization

The store-operated calcium channels in cancer metastasis from cell migration invasion to metastatic colonization

ORAI channels and cancer

The Number and Position of Orai3 Units within Heteromeric Store-Operated Ca2+ Channels Alter the Pharmacology of ICRAC

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