dc.creator | López, Jose J. | es |
dc.creator | Siegfried, Geraldine | es |
dc.creator | Cantonero, Carlos | es |
dc.creator | Soulet, Fabienne | es |
dc.creator | Descarpentrie, Jean | es |
dc.creator | Smani Hajami, Tarik | es |
dc.date.accessioned | 2021-05-20T11:18:04Z | |
dc.date.available | 2021-05-20T11:18:04Z | |
dc.date.issued | 2021-04-01 | |
dc.identifier.citation | López, J.J., Siegfried, G., Cantonero, C., Soulet, F., Descarpentrie, J. y Smani Hajami, T. (2021). Furin prodomain ppfurin enhances ca2+ entry through orai and trpc6 channels’ activation in breast cancer cells. Cancers, 13 (7) | |
dc.identifier.issn | 2072-6694(electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/109109 | |
dc.description.abstract | Furin, a proprotein convertase that belongs to a family of Ca2+-dependent serine peptidases, is involved in the maturation of a variety of proproteins, including growth factors, receptors and differentiation factors, adhesion molecules and proteases. Furin have been associated with tumorigenesis and tumor progression and metastasis; therefore, it has been hypothesized that Furin may constitute a new potential target for cancer therapy. In triple negative breast cancer cells, inhibition of Furin by the prodomain ppFurin results in enhancement of Ca2+ influx, which involves both the increase of store-operated calcium entry (SOCE) and the activation of constitutive Ca2+ entry. The latter involves the activation of Orai and TRPC6 channels, while the increase of SOCE observed in ppFurin-expressing cells is entirely dependent on Orai channels. As a result, ppFurin expression reduces triple negative breast cancer cell viability and ability to migrate and enhances their sensitization to hydrogen peroxide-induced apoptosis. | es |
dc.description.abstract | The intracellular calcium concentration ([Ca2+]i
) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca2+]i homeostasis is involved in
tumor initiation and progression. Here we showed that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced
store-operated calcium entry (SOCE) and reduced the cell malignant phenotype. Expression of
ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits
Furin activity as assessed by in vitro digestion assays. Accordingly, cell transfection experiments
revealed that the ppFurin-expressing cells are unable to adequately process the proprotein convertase
(PC) substrates vascular endothelial growth factor C (proVEGF-C) and insulin-like growth factor-1
receptor (proIGF-1R). Compared to MDA-MB-435 cells, expression of ppFurin in MDA-MB-231
and BT20 cells significantly enhanced SOCE and induced constitutive Ca2+ entry. The enhanced
SOCE is impaired by inhibition of Orai channels while the constitutive Ca2+ entry is attenuated
by silencing or inhibition of TRPC6 or inhibition of Orai channels. Analysis of TRPC6 activation
revealed its upregulated tyrosine phosphorylation in ppFurin-expressing MDA-MB-231 cells. In
addition, while ppFurin had no effect on MDA-MB-435 cell viability, in MDA-MB-231 cells ppFurin
expression reduced their viability and ability to migrate and enhanced their sensitization to the
apoptosis inducer hydrogen peroxide and similar results were observed in BT20 cells. These findings
suggest that Furin inhibition by ppFurin may be a useful strategy to interfere with Ca2+ mobilization, leading to breast cancer cells’ malignant phenotype repression and reduction of their resistance to
treatments. | es |
dc.description.sponsorship | Junta de Extremadura-Fondo Europeo de Desarrollo Regional IB16046 y GR18061 | es |
dc.description.sponsorship | Junta de Extremadura TA18011 | es |
dc.description.sponsorship | SIRIC-Brio, La Ligue Contre le Cancer y Region Nouvelle Aquitania a A.M.K. y por PID2019-104084GB-C21 y PID2019-104084GB-C22 / AEI / 10.13039 / 501100011033, | es |
dc.format | application/pdf | es |
dc.format.extent | 21 p. | es |
dc.language.iso | eng | es |
dc.publisher | MDPI | es |
dc.relation.ispartof | Cancers, 13 (7) | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Furin | es |
dc.subject | PpFurin | es |
dc.subject | Breast cancer | es |
dc.subject | Calcium | es |
dc.subject | SOCE | es |
dc.subject | TRPC6 | es |
dc.subject | Viability | es |
dc.subject | Migration | es |
dc.title | Furin prodomain ppfurin enhances ca2+ entry through orai and trpc6 channels’ activation in breast cancer cells | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica | es |
dc.relation.projectID | IB16046 | es |
dc.relation.projectID | GR18061 | es |
dc.relation.projectID | TA18011 | es |
dc.relation.publisherversion | https://doi.org/10.3390/cancers13071670 | es |
dc.identifier.doi | 10.3390/cancers13071670 | es |
dc.journaltitle | Cancers | es |
dc.publication.volumen | 13 | es |
dc.publication.issue | 7 | es |