Orai1 and STIM1 Are Critical for Breast Tumor Cell Migration and Metastasis

Yang, Shung‐Haur; Zhang, J. Jillian; Huang, Xin

doi:10.1016/j.ccr.2008.12.019

Cited by 628 publications

(731 citation statements)

References 58 publications

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“…We used two mouse models to test the effect of G2 on tumour metastasis. In the first orthotropic spontaneous tumour metastasis mouse model, 4T1 mouse breast tumour cells were injected into the orthotropic site (the mammary gland) and then the metastasis to the lung was monitored 35,52,53 (Fig. 6a).…”

Section: Resultsmentioning

confidence: 99%

“…Seven days after implantation of 4T1 tumour cells, we injected the mice with control solvent or G2 (daily at 100 mg kg À 1 ). After 18 days, the mice were killed and examined for metastasis in the lungs 35,52,53 . Whereas mice injected with control solvent exhibited large numbers of metastasized 4T1 cells in the lungs, the number of metastasized 4T1 cells in the lungs of mice treated with G2 was reduced by B95% (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the second experimental metastasis mouse model, MDA-MB-231 human breast tumour cells were retrovirally infected with a triple-fusion protein reporter construct encoding herpes simplex virus thymidine kinase 1, GFP and firefly luciferase 53,55 . These cells were injected into the tail vein of immuno-deficient mice (NOD-SCID mice).…”

Section: Resultsmentioning

confidence: 99%

“…These cells were injected into the tail vein of immuno-deficient mice (NOD-SCID mice). The extravasation and lung colonization of tumour cells were monitored by non-invasive bioluminescence imaging 35,52,53 (Fig. 6b,c).…”

Section: Resultsmentioning

confidence: 99%

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Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

et al. 2015

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One of the key steps during tumour metastasis is tumour cell migration and invasion, which require actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are the filopodia, which act like cell sensory organs to communicate with the extracellular microenvironment and participate in fundamental cell functions such as cell adhesion, spreading and migration in the three-dimensional environment. Fascin is the main actin-bundling protein in filopodia. Using high-throughput screening, here we identify and characterize small molecules that inhibit the actin-bundling activity of fascin. Focusing on one such inhibitor, we demonstrate that it specifically blocks filopodial formation, tumour cell migration and invasion in vitro, and metastasis in vivo. Hence, target-specific anti-fascin agents have a therapeutic potential for cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

et al. 2015

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“…In breast cancer cells store-operated Ca 2+ channels are essential for migration and invasion [58], and epithelial-mesenchymal transition can also be regulated through SOCE in MCF-7 cells [59]. Further, SOCE is involved in the apoptosis-inducing effect of butyrate in colon cancer cells [60].…”

Section: Discussionmentioning

confidence: 99%

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

et al. 2014

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The expression of the plasma membrane Ca 2+ ATPase (PMCA) isoforms is altered in several types of cancer cells suggesting that they are involved in cancer progression. In this study we induced differentiation of MCF-7 breast cancer cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13-acetate (PMA) and found strong upregulation of PMCA4b protein expression in response to these treatments. Furthermore, combination of HDACis with PMA augmented cell differentiation and further enhanced PMCA4b expression both at mRNA and protein levels. Immunocytochemical analysis revealed that the upregulated protein was located mostly in the plasma membrane. To examine the functional consequences of elevated PMCA4b expression, the characteristics of intracellular Ca 2+ signals were investigated before and after differentiation inducing treatments, and also in cells overexpressing PMCA4b. The increased PMCA4b expression -either by treatment or overexpression -led to enhanced Ca 2+ clearance from the stimulated cells. We found pronounced PMCA4 protein expression in normal breast tissue samples highlighting the importance of this pump for the maintenance of mammary epithelial Ca 2+ homeostasis. These results suggest that modulation of Ca 2+ signaling by enhanced PMCA4b expression may contribute to normal development of breast epithelium and may be lost in cancer.3

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NCS‐1 expression is higher in basal breast cancers and regulates calcium influx and cytotoxic responses to doxorubicin

et al. 2019

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Neuronal calcium sensor-1 (NCS-1) is a positive modulator of IP 3 receptors and was recently associated with poorer survival in breast cancers. However, the association between NCS-1 and breast cancer molecular subtypes and the effects of NCS-1 silencing on calcium (Ca 2+ ) signaling in breast cancer cells remain unexplored. Herein, we report for the first time an increased expression of NCS-1 in breast cancers of the basal molecular subtype, a subtype associated with poor prognosis. Using MDA-MB-231 basal breast cancer cells expressing the GCaMP6m Ca 2+ indicator, we showed that NCS-1 silencing did not result in major changes in cytosolic free Ca 2+ increases as a result of endoplasmic reticulum Ca 2+ store mobilization. However, NCS-1 silencing suppressed unstimulated basal Ca 2+ influx. NCS-1 silencing in MDA-MB-231 cells also promoted necrotic cell death induced by the chemotherapeutic drug doxorubicin (1 µM). The effect of NCS-1 silencing on cell death was phenocopied by silencing of ORAI1, a Ca 2+ store-operated Ca 2+ channel that maintains Ca 2+ levels in the endoplasmic reticulum Ca 2+ store and whose expression was significantly positively correlated with NCS-1 in clinical breast cancer samples. This newly identified association between NCS-1 and basal breast cancers, together with the identification of the role of NCS-1 in the regulation of the effects of doxorubicin in MDA-MB-231 breast cancer cells, suggests that NCS-1 and/or pathways regulated by NCS-1 may be important in the treatment of basal breast cancers in women.

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Orai1 and STIM1 Are Critical for Breast Tumor Cell Migration and Metastasis

Cited by 628 publications

References 58 publications

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

NCS‐1 expression is higher in basal breast cancers and regulates calcium influx and cytotoxic responses to doxorubicin

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