dc.contributor.author | Sikandar, SS | |
dc.contributor.author | Gulati, GS | |
dc.contributor.author | Antony, J | |
dc.contributor.author | Fetter, I | |
dc.contributor.author | Kuo, AH | |
dc.contributor.author | Ho, WHD | |
dc.contributor.author | Haro-Acosta, V | |
dc.contributor.author | Das, S | |
dc.contributor.author | Steen, CB | |
dc.contributor.author | Pereira, TA | |
dc.contributor.author | Qian, D | |
dc.contributor.author | Beachy, PA | |
dc.contributor.author | Dirbas, FM | |
dc.contributor.author | Red-Horse, K | |
dc.contributor.author | Rabbitts, TH | |
dc.contributor.author | Thiery, JP | |
dc.contributor.author | Newman, AM | |
dc.contributor.author | Clarke, MF | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-01-31T09:56:45Z | |
dc.date.available | 2023-01-31T09:56:45Z | |
dc.date.issued | 2022-11-11 | |
dc.identifier.citation | Science Advances, 2022, 8 (45), pp. eabm3548 - | |
dc.identifier.issn | 2375-2548 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5670 | |
dc.identifier.eissn | 2375-2548 | |
dc.identifier.eissn | 2375-2548 | |
dc.identifier.doi | 10.1126/sciadv.abm3548 | |
dc.description.abstract | Metastasis is responsible for most breast cancer-related deaths; however, identifying the cellular determinants of metastasis has remained challenging. Here, we identified a minority population of immature THY1+/VEGFA+ tumor epithelial cells in human breast tumor biopsies that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher abundance of LMO2+ basal cells correlated with tumor endothelial content and predicted poor distant recurrence-free survival in patients. Using MMTV-PyMT/Lmo2CreERT2 mice, we demonstrated that Lmo2 lineage-traced cells integrate into the vasculature and have a higher propensity to metastasize. LMO2 knockdown in human breast tumors reduced lung metastasis by impairing intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 binds to STAT3 and is required for STAT3 activation by tumor necrosis factor-α and interleukin-6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis. | |
dc.format | Print-Electronic | |
dc.format.extent | eabm3548 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | |
dc.relation.ispartof | Science Advances | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Animals | |
dc.subject | Female | |
dc.subject | Breast Neoplasms | |
dc.subject | Lung Neoplasms | |
dc.subject | Signal Transduction | |
dc.subject | Proto-Oncogene Proteins | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | LIM Domain Proteins | |
dc.title | Identification of a minority population of LMO2+ breast cancer cells that integrate into the vasculature and initiate metastasis. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-09-22 | |
dc.date.updated | 2023-01-31T09:54:37Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1126/sciadv.abm3548 | |
rioxxterms.licenseref.startdate | 2022-11-11 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36351009 | |
pubs.issue | 45 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Chromosomal Translocations and Intracellular Antibody Therapeutics | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1126/sciadv.abm3548 | |
pubs.volume | 8 | |
icr.researchteam | Chr Trans & Intra Ab Ther | |
dc.contributor.icrauthor | Rabbitts, Terence | |
icr.provenance | Deposited by Mr Arek Surman on 2023-01-31. Deposit type is initial. No. of files: 1. Files: sciadv.abm3548.pdf | |