Please use this identifier to cite or link to this item:
https://doi.org/10.1002/emmm.201100150
DC Field | Value | |
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dc.title | Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer | |
dc.contributor.author | Soon, W.W. | |
dc.contributor.author | Miller, L.D. | |
dc.contributor.author | Black, M.A. | |
dc.contributor.author | Dalmasso, C. | |
dc.contributor.author | Chan, X.B. | |
dc.contributor.author | Pang, B. | |
dc.contributor.author | Ong, C.W. | |
dc.contributor.author | Salto-Tellez, M. | |
dc.contributor.author | Desai, K.V. | |
dc.contributor.author | Liu, E.T. | |
dc.date.accessioned | 2014-11-26T07:43:39Z | |
dc.date.available | 2014-11-26T07:43:39Z | |
dc.date.issued | 2011-08 | |
dc.identifier.citation | Soon, W.W., Miller, L.D., Black, M.A., Dalmasso, C., Chan, X.B., Pang, B., Ong, C.W., Salto-Tellez, M., Desai, K.V., Liu, E.T. (2011-08). Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer. EMBO Molecular Medicine 3 (8) : 451-464. ScholarBank@NUS Repository. https://doi.org/10.1002/emmm.201100150 | |
dc.identifier.issn | 17574676 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/109253 | |
dc.description.abstract | Secretory factors that drive cancer progression are attractive immunotherapeutic targets. We used a whole-genome data-mining approach on multiple cohorts of breast tumours annotated for clinical outcomes to discover such factors. We identified Serine protease inhibitor Kazal-type 1 (SPINK1) to be associated with poor survival in estrogen receptor-positive (ER+) cases. Immunohistochemistry showed that SPINK1 was absent in normal breast, present in early and advanced tumours, and its expression correlated with poor survival in ER+ tumours. In ER- cases, the prognostic effect did not reach statistical significance. Forced expression and/or exposure to recombinant SPINK1 induced invasiveness without affecting cell proliferation. However, down-regulation of SPINK1 resulted in cell death. Further, SPINK1 overexpressing cells were resistant to drug-induced apoptosis due to reduced caspase-3 levels and high expression of Bcl2 and phospho-Bcl2 proteins. Intriguingly, these anti-apoptotic effects of SPINK1 were abrogated by mutations of its protease inhibition domain. Thus, SPINK1 affects multiple aggressive properties in breast cancer: survival, invasiveness and chemoresistance. Because SPINK1 effects are abrogated by neutralizing antibodies, we suggest that SPINK1 is a viable potential therapeutic target in breast cancer. © 2011 EMBO Molecular Medicine. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1002/emmm.201100150 | |
dc.source | Scopus | |
dc.subject | Breast cancer | |
dc.subject | Cancer therapy | |
dc.subject | Distant metastasis-free survival | |
dc.subject | Expression microarrays | |
dc.subject | Oncogenes | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | PATHOLOGY | |
dc.description.doi | 10.1002/emmm.201100150 | |
dc.description.sourcetitle | EMBO Molecular Medicine | |
dc.description.volume | 3 | |
dc.description.issue | 8 | |
dc.description.page | 451-464 | |
dc.identifier.isiut | 000294359400004 | |
Appears in Collections: | Staff Publications Elements |
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