Furin Prodomain ppFurin Enhances Ca2+ Entry Through Orai and TRPC6 Channels’ Activation in Breast Cancer Cells
dc.contributor.author | López, Jose J. | |
dc.contributor.author | Siegfried, Geraldine | |
dc.contributor.author | Cantonero, Carlos | |
dc.contributor.author | Soulet, Fabienne | |
dc.contributor.author | Descarpentrie, Jean | |
dc.contributor.author | Smani, Tarik | |
dc.contributor.author | Badiola Echaburu, Iker ![]() | |
dc.contributor.author | Pernot, Simon | |
dc.contributor.author | Evrard, Serge | |
dc.contributor.author | Rosado, Juan A. | |
dc.contributor.author | Khatib, Abdel-Majid | |
dc.date.accessioned | 2021-04-20T09:04:37Z | |
dc.date.available | 2021-04-20T09:04:37Z | |
dc.date.issued | 2021-04-01 | |
dc.identifier.citation | Cancers 13(7) : (2021) // Article ID 1670 | es_ES |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | http://hdl.handle.net/10810/51099 | |
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_ES |
dc.description.sponsorship | This research was funded by SIRIC-Brio, La Ligue Contre le Cancer and Region Nouvelle Aquitaine to A.M.K. and by PID2019-104084GB-C21 and PID2019-104084GB-C22/AEI/10.13039/501100011033, MICINN (Grant BFU2016-74932-C2) and Junta de Extremadura-Fondo Europeo de Desarrollo Regional (FEDER; Grants IB16046 and GR18061) to J.A.R. and T.S. J.J.L. is supported by a contract from Junta de Extremadura (TA18011). C.C. is supported by a contract from Junta de Extremadura—FEDER. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-104084GB-C21 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-104084GB-C22 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/BFU2016-74932-C2 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | furin | es_ES |
dc.subject | ppFurin | es_ES |
dc.subject | breast cancer | es_ES |
dc.subject | calcium | es_ES |
dc.subject | SOCE | es_ES |
dc.subject | TRPC6 | es_ES |
dc.subject | viability | es_ES |
dc.subject | migration | es_ES |
dc.title | Furin Prodomain ppFurin Enhances Ca2+ Entry Through Orai and TRPC6 Channels’ Activation in Breast Cancer Cells | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2021-04-09T13:47:51Z | |
dc.rights.holder | 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2072-6694/13/7/1670/htm | es_ES |
dc.identifier.doi | 10.3390/cancers13071670 | |
dc.departamentoes | Biología celular e histología | |
dc.departamentoeu | Zelulen biologia eta histologia |
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Except where otherwise noted, this item's license is described as 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).