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dc.contributor.authorGastaldi, S
dc.contributor.authorSassi, F
dc.contributor.authorAccornero, P
dc.contributor.authorTorti, D
dc.contributor.authorGalimi, F
dc.contributor.authorMigliardi, G
dc.contributor.authorMolyneux, G
dc.contributor.authorPerera, T
dc.contributor.authorComoglio, PM
dc.contributor.authorBoccaccio, C
dc.contributor.authorSmalley, MJ
dc.contributor.authorBertotti, A
dc.contributor.authorTrusolino, L
dc.date.accessioned2018-08-06T14:13:27Z
dc.date.issued2013-03-14
dc.identifier11
dc.identifier.citationONCOGENE, 2013, 32 pp. 1428 - 1440
dc.identifier.issn0950-9232
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2275
dc.identifier.doi10.1038/onc.2012.154
dc.description.abstractBasal-like breast cancer is an aggressive subtype of mammary carcinoma. Despite expressing basal markers, typical of mammary stem cells, this tumor has been proposed to originate from luminal progenitors, which are downstream of stem cells along the mammary epithelial hierarchy. This suggests that committed luminal progenitors may reacquire basal, stem-like characteristics, but the mechanisms that regulate this transition remain unclear. Using mouse models, we found that luminal progenitors express high levels of the Met receptor for hepatocyte growth factor (HGF), as compared with the other mammary epithelial sub-populations. Constitutive activation of Met led luminal progenitors to attain stem cell properties, including enhanced clonogenic activity in vitro and de novo ability to reconstitute mammary glands in repopulation assays in vivo. Moreover, in response to Met signaling, luminal progenitors gave rise to hyperplastic ductal morphogenesis and preferentially underwent basal lineage commitment at the expense of luminal cell-fate specification. Opposite and symmetric results were produced by systemic pharmacological inhibition of Met. Hence, Met signaling targets luminal progenitors for expansion, impairs their differentiation toward the mature luminal phenotype and enables their commitment toward the basal lineage. These results emphasize a critical role for Met in promoting deregulated proliferation and basal plasticity of normal luminal progenitors in the mammary gland, a complex of events that may be required for sustaining the functional and phenotypic properties of basal-like breast tumors. Oncogene (2013) 32, 1428-1440; doi:10.1038/onc.2012.154; published online 7 May 2012
dc.format.extent1428 - 1440
dc.languageeng
dc.language.isoeng
dc.publisherNATURE PUBLISHING GROUP
dc.titleMet signaling regulates growth, repopulating potential and basal cell-fate commitment of mammary luminal progenitors: implications for basal-like breast cancer
dc.typeJournal Article
rioxxterms.versionofrecord10.1038/onc.2012.154
rioxxterms.licenseref.startdate2013-03-14
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfONCOGENE
pubs.notesaffiliation: Trusolino, L (Reprint Author), Inst Canc Res & Treatment IRCC, Mol Pharmacol Lab, Str Prov 142,Km 3-95, I-10060 Candiolo, Italy. Gastaldi, S.; Sassi, F.; Torti, D.; Galimi, F.; Migliardi, G.; Bertotti, A.; Trusolino, L., Inst Canc Res & Treatment IRCC, Mol Pharmacol Lab, I-10060 Candiolo, Italy. Gastaldi, S.; Sassi, F.; Torti, D.; Migliardi, G.; Comoglio, P. M.; Boccaccio, C.; Bertotti, A.; Trusolino, L., Univ Turin, Sch Med, Dept Oncol Sci, Candiolo, Italy. Accornero, P., Univ Torino, Sch Vet Med, Dept Vet Morphophysiol, Grugliasco, Italy. Molyneux, G.; Smalley, M. J., Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. Perera, T., Janssen Res & Dev, Beerse, Belgium. Comoglio, P. M., Inst Canc Res & Treatment IRCC, Div Mol Clin Oncol, I-10060 Candiolo, Italy. Boccaccio, C., Inst Canc Res & Treatment IRCC, Lab Canc Stem Cell Biol, I-10060 Candiolo, Italy. keywords: Met tyrosine kinase receptor; mammary stem cells; mammary morphogenesis; basal-like breast cancer; cell-fate determination; mammary tumorigenesis keywords-plus: RECEPTOR TYROSINE KINASE; EPITHELIAL STEM-CELLS; ADULT HUMAN BREAST; GLAND DEVELOPMENT; LUNG-CANCER; C-MET; DUCTAL MORPHOGENESIS; MOLECULAR PORTRAITS; ONCOGENE ADDICTION; EGF RECEPTOR research-areas: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity web-of-science-categories: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity author-email: [email protected] [email protected] researcherid-numbers: Smalley, Matthew/M-7000-2015 orcid-numbers: Smalley, Matthew/0000-0001-9540-1146 Boccaccio, Carla/0000-0003-2620-9083 Bertotti, Andrea/0000-0001-8196-7608 Comoglio, Paolo/0000-0002-7056-5328 funding-acknowledgement: Janssen pharmaceutical companies; AIRC, Associazione Italiana per la Ricerca sul Cancro (IG project) [10116]; MIUR-FIRB, Fondo per gli Investimenti della Ricerca di Base - Futuro in Ricerca; FPRC, Fondazione Piemontese per la Ricerca sul Cancro; Breakthrough Breast Cancer; United Kingdom National Health Service funding-text: T Perera is an employee of Janssen pharmaceutical companies of Johnson & Johnson. PM Comoglio receives research grants from Janssen pharmaceutical companies. The other authors declare no potential conflicts of interest.; We thank Erica Lantelme for help with FACS sorting; Noemi Cavalera, Claudio Isella, Howard Kendrick, Simonetta Leto, Barbara Lupo, Paolo Luraghi, Fiona-Ann Magnay, Barbara Martinoglio, Enzo Medico, Roberta Porporato and Eugenia Zanella for help with experiments, discussion and sharing reagents; Fabrizio Maina, Laura Tarditi and Tuti Werdiningsih for animal husbandry; Raffaella Albano, Stefania Giove and Laura Palmas for technical assistance; Antonella Cignetto, Daniela Gramaglia and Francesca Natale for secretarial assistance. This work was supported by AIRC, Associazione Italiana per la Ricerca sul Cancro (IG project 10116 to LT); MIUR-FIRB, Fondo per gli Investimenti della Ricerca di Base - Futuro in Ricerca (AB); FPRC, Fondazione Piemontese per la Ricerca sul Cancro (LT); Breakthrough Breast Cancer and United Kingdom National Health Service funding to the National Institute for Health Research Biomedical Research Centre (MJS). number-of-cited-references: 60 times-cited: 32 usage-count-last-180-days: 0 usage-count-since-2013: 13 journal-iso: Oncogene doc-delivery-number: 110OZ unique-id: ISI:000316455600009 da: 2018-08-06
pubs.notesNot known
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Mammary Stem Cells
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Mammary Stem Cells
pubs.volume32
pubs.embargo.termsNot known
icr.researchteamMammary Stem Cellsen_US
dc.contributor.icrauthorSmalley, Matthewen
dc.contributor.icrauthorMolyneux, Gen


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