dc.creator | Smani Hajami, Tarik | es |
dc.creator | Falcón Boyano, Débora | es |
dc.date.accessioned | 2020-03-26T16:31:02Z | |
dc.date.available | 2020-03-26T16:31:02Z | |
dc.date.issued | 2019-10-23 | |
dc.identifier.citation | Smani Hajami, T. y Falcón Boyano, D. (2019). Adenylyl Cyclase Type 8 Overexpression Impairs Phosphorylation-Dependent Orai1 Inactivation and Promotes Migration in MDA-MB-231 Breast Cancer Cells.. Cancers, 11 (11), 1-24. | |
dc.identifier.issn | 2072-6694 | es |
dc.identifier.uri | https://hdl.handle.net/11441/94591 | |
dc.description.abstract | Orai1 plays a major role in store-operated Ca 2+ entry (SOCE) in triple-negative breast
cancer (TNBC) cells. This channel is inactivated via different mechanisms, including protein kinase
C (PKC) and protein kinase A (PKA)-dependent phosphorylation at Ser-27 and Ser-30 or Ser-34,
respectively, which shapes the Ca 2+ responses to agonists. The Ca 2+ calmodulin-activated adenylyl
cyclase type 8 (AC8) was reported to interact directly with Orai1, thus mediating a dynamic
interplay between the Ca 2+ - and cyclic adenosine monophosphate (cAMP)-dependent signaling
pathways. Here, we show that the breast cancer cell lines MCF7 and MDA-MB-231 exhibit enhanced
expression of Orai1 and AC8 as compared to the non-tumoral breast epithelial MCF10A cell line. In
these cells, AC8 interacts with the Orai1α variant in a manner that is not regulated by Orai1
phosphorylation. AC8 knockdown in MDA-MB-231 cells, using two different small interfering
RNAs (siRNAs), attenuates thapsigargin (TG)-induced Ca 2+ entry and also Ca 2+ influx mediated by
co-expression of Orai1 and the Orai1-activating small fragment (OASF) of STIM1 (stromal
interaction molecule-1). Conversely, AC8 overexpression enhances SOCE, as well as Ca 2+ entry, in
cells co-expressing Orai1 and OASF. In MDA-MB-231 cells, we found that AC8 overexpression
reduces the Orai1 phosphoserine content, thus suggesting that AC8 interferes with Orai1 serine
phosphorylation, which takes place at residues located in the AC8-binding site. Consistent with this,
the subset of Orai1 associated with AC8 in naïve MDA-MB-231 cells is not phosphorylated in serine
residues in contrast to the AC8-independent Orai1 subset. AC8 expression knockdown attenuates
migration of MCF7 and MDA-MB-231 cells, while this maneuver has no effect in the MCF10A cell
line, which is likely attributed to the low expression of AC8 in these cells. We found that AC8 is
required for FAK (focal adhesion kinase) phosphorylation in MDA-MB-231 cells, which might
explain its role in cell migration. Finally, we found that AC8 is required for TNBC cell proliferation.
These findings indicate that overexpression of AC8 in breast cancer MDA-MB-231 cells impairs the
phosphorylation-dependent Orai1 inactivation, a mechanism that might support the enhanced
ability of these cells to migrate. | es |
dc.description.sponsorship | Ministerio de Asuntos Económicos y de Transformación Digital. | es |
dc.description.sponsorship | Fondo Europeo de Desarrollo Regional Grants. | es |
dc.description.sponsorship | Junta de Extremadura. | es |
dc.description.sponsorship | Juan de la Cierva (Ministro de Industria, Economía y Competitividad). | es |
dc.format | application/pdf | es |
dc.format.extent | 25 | es |
dc.language.iso | eng | es |
dc.relation.ispartof | Cancers, 11 (11), 1-24. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | orai1α | es |
dc.subject | adenylyl cyclase 8 | es |
dc.subject | store-operated calcium entry | es |
dc.subject | breast cancer cells | es |
dc.subject | migration | es |
dc.title | Adenylyl Cyclase Type 8 Overexpression Impairs Phosphorylation-Dependent Orai1 Inactivation and Promotes Migration in MDA-MB-231 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 | BFU2016-74932-C2-1-P, BFU2013-45564-C2, BFU2016-74932-C2 | es |
dc.relation.projectID | B16046, GR15029, GR18061 | es |
dc.relation.publisherversion | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893434/ | es |
dc.identifier.doi | 10.3390/cancers11111624 | es |
dc.contributor.group | Universidad de Sevilla. CTS-200: Transplante Corazón, Conservación Corazón Donante. | es |
dc.journaltitle | Cancers | es |
dc.publication.volumen | 11 | es |
dc.publication.issue | 11 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 24 | es |