Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/173254
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Cuyàs, Elisabet | - |
dc.contributor.author | Gumuzio, Juan | - |
dc.contributor.author | Verdura, Sara | - |
dc.contributor.author | Brunet, Joan | - |
dc.contributor.author | Bosch Barrera, Joaquim | - |
dc.contributor.author | Martín Castillo, Begoña | - |
dc.contributor.author | Alarcón Cor, Tomás | - |
dc.contributor.author | Encinar, José Antonio | - |
dc.contributor.author | Martin, Ángel G. | - |
dc.contributor.author | Menendez, Javier A. | - |
dc.date.accessioned | 2021-01-20T16:49:54Z | - |
dc.date.available | 2021-01-20T16:49:54Z | - |
dc.date.issued | 2020-01-01 | - |
dc.identifier.uri | http://hdl.handle.net/2445/173254 | - |
dc.description.abstract | SOX2 is a core pluripotency-associated transcription factor causally related to cancer initiation, aggressiveness, and drug resistance by driving the self-renewal and seeding capacity of cancer stem cells (CSC). Here, we tested the ability of the clinically proven inhibitor of the lysine-specific demethylase 1 (LSD1/KDM1A) iadademstat (ORY-100) to target SOX2-driven CSC in breast cancer. Iadademstat blocked CSC-driven mammosphere formation in breast cancer cell lines that are dependent on SOX2 expression to maintain their CSC phenotype. Iadademstat prevented the activation of an LSD1-targeted stemness-specific SOX2 enhancer in CSC-enriched 3-dimensional spheroids. Using high-throughput transcriptional data available from the METABRIC dataset, high expression of SOX2 was significantly more common in luminal-B and HER2-enriched subtypes according to PAM50 classifier and in IntClust1 (high proliferating luminal-B) and IntClust 5 (luminal-B and HER2-amplified) according to integrative clustering. Iadademstat significantly reduced mammospheres formation by CSC-like cells from a multidrug-resistant luminal-B breast cancer patient-derived xenograft but not of those from a treatment-naive luminal-A patient. Iadademstat reduced the expression of SOX2 in luminal-B but not in luminal-A mammospheres, likely indicating a selective targeting of SOX2-driven CSC. The therapeutic relevance of targeting SOX2-driven breast CSC suggests the potential clinical use of iadademstat as an epigenetic therapy in luminal-B and HER2-positive subtypes. | - |
dc.format.extent | 20 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Impact Journals Llc. | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.18632/aging.102887 | - |
dc.relation.ispartof | Aging-us, 2020, vol. 12, num. 6, p. 4794-4814 | - |
dc.relation.uri | https://doi.org/10.18632/aging.102887 | - |
dc.rights | cc by (c) Cuyàs et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | - |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Epigenètica | - |
dc.subject.classification | Càncer de mama | - |
dc.subject.other | Epigenetics | - |
dc.subject.other | Breast cancer | - |
dc.title | The LSD1 inhibitor iadademstat (ORY-1001) targets SOX2-driven breast cancer stem cells: a potential epigenetic therapy in luminal-B and HER2-positive breast cancer subtypes | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2020-12-21T13:12:04Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32191225 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
CuyasE.pdf | 2.14 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License