Store-Independent Calcium Entry and Related Signaling Pathways in Breast Cancer

Chamlali, Mohamed; Rodat-Despoix, Lise; Ouadid-Ahidouch, Halima

doi:10.3390/genes12070994

Cited by 11 publications

(8 citation statements)

References 62 publications

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“…However, the biological functions of ZNF791 and MED18 in BRCA are largely unknown, making it impossible to infer the plausibility of associations between the two sites and BRCA survival. Moreover, the cellular pathway clearly demonstrated that AIRS was associated with several signaling pathways, such as oxidative phosphorylation ( 33 ), proteasome ( 34 ), and calcium signaling pathway ( 35 ). These pathways are all promising targets for the treatment of BRCA, which suggests the AIRS as new targets for BRCA treatment.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients

et al. 2022

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BackgroundAdenosine-to-inosine RNA editing (ATIRE) is increasingly being used to characterize cancer. However, no studies have been conducted to identify an ATIRE signature for predicting cancer survival.MethodsBreast cancer (BRCA) samples with ATIRE profiles from The Cancer Genome Atlas were divided into training (n = 452) and internal validation cohorts (n = 311), and 197 additional BRCA patients were recruited as an external validation cohort. The ATIRE signature for BRCA overall survival (OS) and disease-free survival (DFS) were identified using forest algorithm analysis and experimentally verified by direct sequencing. An ATIRE-based risk score (AIRS) was established with these selected ATIRE sites. Significantly prognostic factors were incorporated to generate a nomogram that was evaluated using Harrell’s C-index and calibration plot for all cohorts.ResultsSeven ATIRE sites were revealed to be associated with both BRCA OS and DFS, of which four sites were experimentally confirmed. Patients with high AIRS displayed a higher risk of death than those with low AIRS in the training (hazard ratio (HR) = 3.142, 95%CI = 1.932–5.111), internal validation (HR = 2.097, 95%CI = 1.123–3.914), and external validation cohorts (HR = 2.680, 95%CI = 1.000–7.194). A similar hazard effect of high AIRS on DFS was also observed. The nomogram yielded Harrell’s C-indexes of 0.816 (95%CI = 0.784–0.847), 0.742 (95%CI = 0.684–0.799), and 0.869 (95%CI = 0.835–0.902) for predicting OS and 0.767 (95%CI = 0.708–0.826), 0.684 (95%CI = 0.605–0.763), and 0.635 (95%CI = 0.566–0.705) for predicting DFS in the three cohorts.ConclusionAIRS nomogram could help to predict OS and DFS of patients with BRCA.

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Section: Discussionmentioning

confidence: 99%

Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients

et al. 2022

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“…To what extent Orai1 proteins have the potential to cause cancerous remodelling is dependent on the cancer type and the particular context [ 31 ]. Furthermore, Ca 2+ is essential for human brain tumour glioblastoma invasion [ 65 ] and for invasive stimuli in breast cancer [ 66 , 67 , 68 ]. Melanoma cells are dependent on Orai1 which plays a central role in cell migration and proliferation [ 69 , 70 ].…”

Section: Calcium and Its Role In Human Diseasesmentioning

confidence: 99%

Science CommuniCa2+tion Developing Scientific Literacy on Calcium: The Involvement of CRAC Currents in Human Health and Disease

Humer¹,

Berlansky²,

Grabmayr³

et al. 2022

Cells

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All human life starts with a calcium (Ca2+) wave. This ion regulates a plethora of cellular functions ranging from fertilisation and birth to development and cell death. A sophisticated system is responsible for maintaining the essential, tight concentration of calcium within cells. Intricate components of this Ca2+ network are store-operated calcium channels in the cells’ membrane. The best-characterised store-operated channel is the Ca2+ release-activated Ca2+ (CRAC) channel. Currents through CRAC channels are critically dependent on the correct function of two proteins: STIM1 and Orai1. A disruption of the precise mechanism of Ca2+ entry through CRAC channels can lead to defects and in turn to severe impacts on our health. Mutations in either STIM1 or Orai1 proteins can have consequences on our immune cells, the cardiac and nervous system, the hormonal balance, muscle function, and many more. There is solid evidence that altered Ca2+ signalling through CRAC channels is involved in the hallmarks of cancer development: uncontrolled cell growth, resistance to cell death, migration, invasion, and metastasis. In this work we highlight the importance of Ca2+ and its role in human health and disease with focus on CRAC channels.

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“…ORAI1 can also be activated distinctly from the canonical Ca 2+ store depletion-mediated STIM1-dependent pathway, referred to as store-independent Ca 2+ entry (SICE) [ 10 ]. SICE includes the activation of ORAI1 by the secretory pathway Ca 2+ -ATPase 2 pump (SPCA2), which is implicated in the promotion of tumorigenesis in breast cancer [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

ORAI1-Regulated Gene Expression in Breast Cancer Cells: Roles for STIM1 Binding, Calcium Influx and Transcription Factor Translocation

Robitaille

Chan

Peters

et al. 2022

IJMS

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A remodeling of calcium homeostasis, including calcium influx via store-operated calcium entry (SOCE), is a feature of breast cancers. SOCE is critical to maintain calcium balance in the endoplasmic reticulum calcium store and is an important mechanism for calcium signaling in a variety of cell types, including breast cancer cells. The canonical mechanism of SOCE is stromal interacting molecule 1 (STIM1)-mediated activation of ORAI. Elevated ORAI1 expression is a feature of basal breast cancer cells. However, the role of ORAI1 in the regulation of transcription in breast cancer cells of the basal molecular subtype is still unclear. Using CRISPR-Cas9 gene editing, ORAI1 protein expression was disrupted in MDA-MB-231 and MDA-MB-468 basal breast cancer cells. The ORAI1 wild-type and mutants were reintroduced into ORAI1 knockout cells to study the role of ORAI1 in gene transcriptional regulation. In the absence of calcium store depletion, ORAI1 regulated PTGS2 in MDA-MB-231 cells, and this was dependent on ORAI1 pore function and STIM1 binding. The activation of SOCE by thapsigargin resulted in ORAI1-dependent increases in IL6 transcription in MDA-MB-468 cells; this was also dependent on ORAI1 pore function and STIM1 binding and was associated with the translocation of NFAT1. Given the upregulation of ORAI1 in basal breast cancer cells, our results provide further evidence that ORAI1 may contribute to cancer progression through regulation of gene expression.

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Store-Independent Calcium Entry and Related Signaling Pathways in Breast Cancer

Cited by 11 publications

References 62 publications

Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients

Development and Validation of a Four Adenosine-to-Inosine RNA Editing Site-Relevant Prognostic Signature for Assessing Survival in Breast Cancer Patients

Science CommuniCa2+tion Developing Scientific Literacy on Calcium: The Involvement of CRAC Currents in Human Health and Disease

ORAI1-Regulated Gene Expression in Breast Cancer Cells: Roles for STIM1 Binding, Calcium Influx and Transcription Factor Translocation

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