Abstract:
:The small heat-shock protein of 27 kDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumour behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, epidermal growth factor receptor (EGFR)-addicted colorectal carcinoma (CRC) DiFi cells and BRAF-addicted CRC COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent. In other cell lines, such as MET-addicted gastric carcinoma MKN45 and EGFR-addicted CRC SW48 lines, where oncogene inhibition only blocked proliferation, HSP27 knockdown made targeted agents switch from cytostatic to cytotoxic activity. Mechanistically, the more the cells were susceptible to HSP27 suppression, the more they were primed for death, as demonstrated by increased levels of mitochondrial outer membrane permeabilization. Priming for death was accompanied by the increase in pro-apoptotic proteins of the BCL2 family and of active caspase-3 and lamin B. Together, these data suggest that oncogene-addicted cells require HSP27 for survival and that HSP27 might interfere with the effectiveness of targeted agents.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Konda JD,Olivero M,Musiani D,Lamba S,Di Renzo MFdoi
10.1002/1878-0261.12042subject
Has Abstractpub_date
2017-06-01 00:00:00pages
599-611issue
6eissn
1574-7891issn
1878-0261journal_volume
11pub_type
杂志文章abstract:INTRODUCTION:Most analyses of high throughput cancer data represent tumors by "atomistic" single-gene properties. Pathifier, a recently introduced method, characterizes a tumor in terms of "coarse grained" pathway-based variables. METHODS:We applied Pathifier to study a very large dataset of 2000 breast cancer samples...
journal_title:Molecular oncology
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.12.001
更新日期:2012-06-01 00:00:00
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journal_title:Molecular oncology
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.05.001
更新日期:2015-10-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12178
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12791
更新日期:2021-01-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12562
更新日期:2019-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2009.01.006
更新日期:2009-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12521
更新日期:2019-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12752
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.04.009
更新日期:2014-10-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.005
更新日期:2016-03-01 00:00:00
abstract::miRNAs in circulating extracellular vesicles (EVs) are promising biomarkers for cancer. However, their diagnostic ability for early-stage non-small-cell lung cancer (NSCLC) is not well known. In this study, the circulating EV miRNAs profiling was initially performed in 36 untreated NSCLC patients and 36 healthy contro...
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更新日期:2020-12-19 00:00:00
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pub_type: 杂志文章
doi:10.1002/1878-0261.12375
更新日期:2018-11-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.011
更新日期:2016-02-01 00:00:00
abstract::Triple-negative breast cancer (TNBC), the most refractory subtype of breast cancer to current treatments, accounts disproportionately for the majority of breast cancer-related deaths. This is largely due to cancer plasticity and the development of cancer stem cells (CSCs). Recently, distinct yet interconvertible mesen...
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pub_type: 杂志文章
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更新日期:2018-04-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
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更新日期:2016-06-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.10.013
更新日期:2015-03-01 00:00:00