Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1

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dc.contributor.authorDiaz, Jorge
dc.contributor.authorAranda, Evelyn
dc.contributor.authorHenriquez, Soledad
dc.contributor.authorQuezada, Marisol
dc.contributor.authorEspinoza, Estefania
dc.contributor.authorLoreto Bravo, Maria
dc.contributor.authorOliva, Barbara
dc.contributor.authorLange, Soledad
dc.contributor.authorVillalon, Manuel
dc.contributor.authorJones, Marius
dc.contributor.authorBrosens, Jan J.
dc.contributor.authorKato, Sumie
dc.contributor.authorCuello, Mauricio A.
dc.contributor.authorKnutson, Todd P.
dc.contributor.authorLange, Carol A.
dc.contributor.authorLeyton, Lisette
dc.contributor.authorOwen, Gareth I.
dc.date.accessioned2024-01-10T12:07:44Z
dc.date.available2024-01-10T12:07:44Z
dc.date.issued2012
dc.description.abstractProgesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women. Journal of Endocrinology (2012) 214, 165-175
dc.description.funderFONDECYT
dc.description.funderFONDEF
dc.description.funderThe Wellcome Trust International Collaboration grant
dc.description.funderFONDECYT-Fondos en Areas Prioritarias
dc.description.funderFogarty International Center-NIH
dc.description.funderIniciativa Cientifica Milenio (ICM)
dc.description.funderFOGARTY INTERNATIONAL CENTER
dc.format.extent11 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1530/JOE-11-0310
dc.identifier.eissn1479-6805
dc.identifier.issn0022-0795
dc.identifier.pubmedidMEDLINE:22593082
dc.identifier.urihttps://doi.org/10.1530/JOE-11-0310
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76318
dc.identifier.wosidWOS:000306558600007
dc.information.autorucCiencias Biológicas;Aranda E ;S/I;15771
dc.information.autorucCiencias Biológicas;Bravo M;S/I;125561
dc.information.autorucMedicina;Cuello M;S/I;80064
dc.information.autorucCiencias Biológicas;Espinoza E ;S/I;132615
dc.information.autorucCiencias Biológicas;Henriquez S ;S/I;158185
dc.information.autorucMedicina;Kato S;S/I;82640
dc.information.autorucCiencias Biológicas;Oliva B ;S/I;1008557
dc.information.autorucCiencias Biológicas;Owen G;S/I;1000459
dc.information.autorucCiencias Biológicas;Quezada M ;S/I;158184
dc.information.autorucCiencias Biológicas;Villalon M;S/I;99264
dc.issue.numero2
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final175
dc.pagina.inicio165
dc.publisherBIOSCIENTIFICA LTD
dc.revistaJOURNAL OF ENDOCRINOLOGY
dc.rightsregistro bibliográfico
dc.subjectEPIDERMAL-GROWTH-FACTOR
dc.subjectTISSUE FACTOR
dc.subjectTHROMBIN RECEPTOR
dc.subjectPROCOAGULANT ACTIVITY
dc.subjectGENE-EXPRESSION
dc.subjectINVASION
dc.subjectKINASE
dc.subjectPHOSPHORYLATION
dc.subjectFAMILY
dc.subjectPAR-1
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleProgesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1
dc.typeartículo
dc.volumen214
sipa.codpersvinculados15771
sipa.codpersvinculados125561
sipa.codpersvinculados80064
sipa.codpersvinculados132615
sipa.codpersvinculados158185
sipa.codpersvinculados82640
sipa.codpersvinculados1008557
sipa.codpersvinculados1000459
sipa.codpersvinculados158184
sipa.codpersvinculados99264
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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