Constitutive calcium entry and cancer: updated views and insights

Mignen, Olivier; Constantin, Bruno; Potier-Cartereau, Marie; Penna, Aubin; Gautier, Mathieu; Guéguinou, Maxime; Renaudineau, Yves; Shoji, Kenji F.; Félix, Romain; Bayet, Elsa; Buscaglia, Paul; Debant, Marjolaine; Chantôme, Aurélie; Vandier, Christophe

doi:10.1007/s00249-017-1216-8

Cited by 43 publications

(53 citation statements)

References 150 publications

(168 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Growing evidence shows that cancer cell hallmarks are strongly regulated by ion channels including Ca 2+ , Mg 2+ , and K + , Na + channels . Thus, we further investigated the effect of extracellular Ca 2+ and Mg 2+ on the migration of prostate cancer cells DU145.…”

Section: Resultsmentioning

confidence: 99%

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

Sun

Schaar

Sukumaran

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Growth factors, such as the transforming growth factor beta (TGFβ), play an important role in promoting metastasis of prostate cancer, thus understanding how TGFβ could induce prostate cancer cell migration may enable us to develop targeted strategies for treatment of advanced metastatic prostate cancer. To more clearly define the mechanism(s) involved in prostate cancer cell migration, we undertook a series of studies utilizing non‐malignant prostate epithelial cells RWPE1 and prostate cancer DU145 and PC3 cells. Our studies show that increased cell migration was observed in prostate cancer cells, which was mediated through epithelial‐to‐mesenchymal transition (EMT). Importantly, addition of Mg2+, but not Ca2+, increased cell migration. Furthermore, TRPM7 expression, which functions as an Mg2+ influx channel, was also increased in prostate cancer cells. Inhibition of TRPM7 currents by 2‐APB, significantly blocked cell migration in both DU145 and PC3 cells. Addition of growth factor TGFβ showed a further increase in cell migration, which was again blocked by the addition of 2‐APB. Importantly, TGFβ addition also significantly increased TRPM7 expression and function, and silencing of TRPM7 negated TGFβ‐induced cell migration along with a decrease in EMT markers showing loss of cell adhesion. Furthermore, resveratrol, which decreases prostate cancer cell migration, inhibited TRPM7 expression and function including TGFβ‐induced cell migration and activation of TRPM7 function. Together, these results suggest that Mg2+ influx via TRPM7 promotes cell migration by inducing EMT in prostate cancer cells and resveratrol negatively modulates TRPM7 function thereby inhibiting prostate cancer metastasis.

show abstract

Section: Resultsmentioning

confidence: 99%

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

Sun

Schaar

Sukumaran

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…In nonexcitable cells, Ca 2+ influx is partly mediated by Ca 2+ ‐selective channels activated by intracellular Ca 2+ store depletion called store‐operated channels (SOCs), and by store‐independent Ca 2+ channels, such as ARC channels (arachidonate‐regulated Ca 2+ channels) . SOC channels are mainly composed of Orai1 subunits, but also composed of TRPC channels in some cell types, supporting less Ca 2+ ‐selective SOCE (store‐operated Ca 2+ entry) . SOCs are activated by endoplasmic reticulum (ER) Ca 2+ depletion, and regulated by STIM1, a Ca 2+ sensor mostly localized at the ER membrane .…”

Section: Introductionmentioning

confidence: 99%

“…However, its implication in calcium signaling has not been fully established . Finally, Orai1 and some TRP are also involved in constitutive Ca 2+ entry and tumor development …”

Section: Introductionmentioning

confidence: 99%

“…11 SOC channels are mainly composed of Orai1 subunits, but also composed of TRPC channels in some cell types, supporting less Ca 2+ -selective SOCE (store-operated Ca 2+ entry). [12][13][14] SOCs are activated by endoplasmic reticulum (ER) Ca 2+ depletion, and regulated by STIM1, a Ca 2+ sensor mostly localized at the ER membrane. 15 STIM1 has been implicated in the activation of both Orai1 and some Ca 2+ -permeable TRPC channels, particularly TRPC1 and TRPC4.…”

Section: Introductionmentioning

confidence: 99%

“…18 Finally, Orai1 and some TRP are also involved in constitutive Ca 2+ entry and tumor development. 14 Several studies and recent reviews have reported that Orai, STIM, and TRP proteins are involved in Ca 2+ signaling dysregulation, contributing to tumorigenesis and metastasis. [19][20][21] Overexpression of Orai1/STIM1, mostly by increasing SOCE, appears to enhance various cancer hallmarks.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy

et al. 2019

View full text Add to dashboard Cite

Background: Several studies had suggested the potential role of calcium signaling in prostate cancer (PCa) prognosis and agressiveness. We aimed to investigate selected proteins contributing to calcium (Ca2+) signaling, (Orai, stromal interaction molecule (STIM), and transient receptor potential (TRP) channels) and involved in cancer hallmarks, as independent predictors of systemic recurrence after radical prostatectomy (RP). Methods: A case‐control study including 112 patients with clinically localized PCa treated by RP between 2002 and 2009 and with at least 6‐years’ follow‐up. Patients were divided into two groups according to the absence or presence of systemic recurrence. Expression levels of 10 proteins involved in Ca2+ signaling (TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, STIM1, STIM2, Orai1, Orai2, and Orai3), were assessed by immunohistochemistry using tissue microarrays (TMAs) constructed from paraffin‐embedded PCa specimens. The level of expression of the various transcripts in PCa was assessed using quantitative polymerase chain reaction (qPCR) analysis. RNA samples for qPCR were obtained from fresh frozen tissue samples of PCa after laser capture microdissection on RP specimens. Relative gene expression was analyzed using the 2−▵▵Ct method. Results: Multivariate analysis showed that increased expression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 was significantly associated with a lower risk of systemic recurrence after RP, independently of the prostate‐specific antigen (PSA) level, percentage of positive biopsies, and surgical margin (SM) status (P = .007, P = .01, P < .001, P = .0065, P = .007, and P = .01, respectively). For TRPC4, TRPV5, and TRPV6, this association was also independent of Gleason score and pT stage. Moreover, overexpression of TRPV6 and Orai2 was significantly associated with longer time to recurrence after RP (P = .048 and .023, respectively). Overexpression of TRPC4, TRPV5, TRPV6, and Orai2 transcripts was observed in group R− (3.71‐, 5.7‐, 1.14‐, and 2.65‐fold increase, respectively). Conclusions: This is the first study to suggest the independent prognostic value of certain proteins involved in Ca2+ influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.

show abstract

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Constitutive calcium entry and cancer: updated views and insights

Cited by 43 publications

References 150 publications

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

TGFβ‐induced epithelial‐to‐mesenchymal transition in prostate cancer cells is mediated via TRPM7 expression

Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy

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

Contact Info

Product

Resources

About