| http://purl.uniprot.org/citations/22006997 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22006997 | http://www.w3.org/2000/01/rdf-schema#comment | "Triple-negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). However, pathways responsible for downregulation of therapeutic receptors, as well as subsequent aggressiveness, remain unknown. In this study, we discovered that lactoferrin (Lf) efficiently downregulates levels of ER-α, PR, and HER-2 in a proteasome-dependent manner in breast cancer cells, and it accounts for the loss of responsiveness to ER- or HER-2-targeted therapies. Furthermore, we found that lactoferrin increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that lactoferrin directly stimulates the transcription of endothelin-1 (ET-1), a secreted proinvasive polypeptide that acts through a specific receptor, ET(A)R, leading to secretion of the bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor-antagonist blocked lactoferrin-dependent motility and invasiveness of breast cancer cells. The physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue lactoferrin and ET-1 levels in patients with TNBC compared with those in ER(+) cases. These findings describe the first physiologically relevant polypeptide as a functional determinant in downregulating all three therapeutic receptors in breast cancer, which uses another secreted ET-1 system to confer invasiveness. Results presented in this article provide proof-of-principle evidence in support of the therapeutic effectiveness of ET-1 receptor antagonist to completely block the lactoferrin-induced motility and invasiveness of the TNBC as well as non-TNBC cells, and thus, open a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-11-1143"xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Kumar R."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Pakala S.B."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Ohshiro K."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Prendergast G.C."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Li D.Q."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Reddy D.N."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Costa L."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Nair V.S."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Ha N.H."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Wallon M."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Lipton A."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Badwe R.A."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Ghanta K.S."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Fuqua S."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/author | "Mudvari P."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/pages | "7259-7269"xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/title | "Lactoferrin-endothelin-1 axis contributes to the development and invasiveness of triple-negative breast cancer phenotypes."xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://purl.uniprot.org/core/volume | "71"xsd:string |
| http://purl.uniprot.org/citations/22006997 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22006997 |
| http://purl.uniprot.org/citations/22006997 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22006997 |