Abstract:
:Resistance to chemotherapy is a serious problem for the successful treatment of ovarian cancer patients but signalling pathways that contribute to this chemoinsensitivity are largely unknown. We demonstrate that the chemotherapeutic drug doxorubicin induces activation of the HER3-PI3K-AKT signalling cascade in ovarian cancer cells. We further show that the induction of this anti-apoptotic signalling pathway is based on upregulated expression of HER3 ligands, their shedding by the metalloprotease ADAM17, and is dependent on the HER2 receptor. The doxorubicin-mediated activation of this important survival cascade can be blocked by the kinase inhibitors lapatinib or erlotinib as well as by the therapeutic monoclonal antibody trastuzumab. Inhibition of the doxorubicin-induced activation of HER3-PI3K-AKT signalling significantly increased apoptosis of ovarian cancer cells. Besides doxorubicin, treatment of cells with cisplatin resulted in activation of the HER3 receptor whereas other chemotherapeutics did not show this effect. The increase in HER3 phosphorylation was detected in well-established ovarian cancer cell lines which originate from patients previously treated with these chemotherapeutic drugs. Based on these results, we postulate that activation of the HER3-PI3K-AKT cascade represents a major mechanism of chemoresistance in ovarian cancer.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Bezler M,Hengstler JG,Ullrich Adoi
10.1016/j.molonc.2012.07.001subject
Has Abstractpub_date
2012-10-01 00:00:00pages
516-29issue
5eissn
1574-7891issn
1878-0261pii
S1574-7891(12)00071-3journal_volume
6pub_type
杂志文章abstract::Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms rema...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12765
更新日期:2020-10-01 00:00:00
abstract::PKN3 is an AGC-family protein kinase implicated in growth of metastatic prostate cancer cells with phosphoinositide 3-kinase pathway deregulation. The molecular mechanism, however, by which PKN3 contributes to malignant growth and tumorigenesis is not well understood. Using orthotopic mouse tumor models, we now show t...
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
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.12.017
更新日期:2014-05-01 00:00:00
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 ca...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12042
更新日期:2017-06-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.07.005
更新日期:2016-10-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12164
更新日期:2018-02-01 00:00:00
abstract::Autophagy, a well-described cellular mechanism for lysosomal degradation of cytoplasmic content, has emerged as a tumour suppression pathway. Recent evidence indicates that the tumour suppressor function of autophagy is mediated by scavenging of damaged oxidative organelles, thereby preventing accumulation of toxic ox...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.05.007
更新日期:2009-08-01 00:00:00
abstract::Ovarian cancer is the most lethal gynecologic malignancy. About 75% of ovarian cancer patients relapse and/or develop chemo-resistant disease after initial response to standard-of-care treatment with platinum-based therapies. HER2 amplifications and overexpression in ovarian cancer are reported to vary, and responses ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12414
更新日期:2019-02-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12785
更新日期:2020-11-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.04.002
更新日期:2016-08-01 00:00:00
abstract::It is well known that different racial groups have significantly different incidence and mortality rates for certain cancers. It has been suggested that biological factors play a major role in these cancer racial disparities. Previous studies on the biological factors contributing to cancer racial disparity have gener...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12799
更新日期:2020-09-13 00:00:00
abstract::Epigenetic silencing of miRNA is a primary mechanism of aberrant miRNA expression in cancer, and hypermethylation of miRNA promoters has been reported to contribute to prostate cancer initiation and progression. Recent data have shown that the miR-193b promoter is hypermethylated in prostate cancer compared with norma...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12536
更新日期:2019-09-01 00:00:00
abstract::Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.013
更新日期:2015-04-01 00:00:00
abstract::Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single-cell molecular analysis is required. We developed the ChimeraX® -i120 platform to facilitate negative enrichment, immunofluorescent labelin...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12876
更新日期:2020-12-10 00:00:00
abstract::Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absen...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.09.001
更新日期:2016-12-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.11.008
更新日期:2015-03-01 00:00:00
abstract::The PI3K/Akt signaling pathway, the most frequently altered signaling system in human cancer, is a crucial inducer of dysregulated proliferation and neoplastic processes; however, few therapeutic strategies using PI3K/Akt inhibitors singly have been shown to be effective. The purpose of this paper was to underline the...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12888
更新日期:2020-12-18 00:00:00
abstract:PURPOSE:DNA analysis by NGS has become important to direct the clinical care of cancer patients. However, NGS is not successful in all cases, and the factors responsible for test failures have not been systematically evaluated. MATERIALS AND METHODS:A series of 1528 solid and hematolymphoid tumor specimens was tested ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.05.004
更新日期:2015-11-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12499
更新日期:2019-07-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12564
更新日期:2019-10-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12533
更新日期:2019-09-01 00:00:00
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journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12110
更新日期:2017-10-01 00:00:00
abstract::The let-7 microRNA (miRNA) family has been implicated in the regulation of diverse cellular processes and disease pathogenesis. In cancer, loss-of-function of let-7 miRNAs has been linked to tumorigenesis via increased expression of target oncogenes. Excessive proliferation rate of tumor cells is often associated with...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.01.005
更新日期:2015-06-01 00:00:00
abstract::Cullin 4B, a member of the Cullins, which serve as scaffolds to facilitate the assembly of E3 ligase complexes, is aberrantly expressed in many cancers, including osteosarcoma. Recently, we observed that CUL4B forms the CRL4BDCAF11 E3 ligase, which specifically ubiquitinates and degrades the cyclin-dependent kinase (C...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12176
更新日期:2018-04-01 00:00:00
abstract::The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1∆IEC ). Male but not female STAT1∆IEC mi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12178
更新日期:2018-04-01 00:00:00
abstract::Tumor growth, especially in the late stage, requires adequate nutrients and rich vasculature, in which PKM2 plays a convergent role. It has been reported that PKM2, together with FOXM1D, is upregulated in late stage colorectal cancer and associated with metastasis; however, their underlying mechanism for promoting tum...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12879
更新日期:2020-12-13 00:00:00
abstract::In our previous study, we identified 1241 loci with somatic copy number alterations in human hepatocellular carcinoma (HCC) using Affymetrix SNP 6.0 arrays, and a putative cancer gene SERPINA5 was uncovered in a novel chromosomal region with recurrent copy number loss at 14q31.1-32.13. The SERPINA5 was reported to be ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.12.003
更新日期:2014-03-01 00:00:00
abstract::Histone deacetylases (HDACs), originally described as histone modifiers, have more recently been demonstrated to target a variety of other proteins unrelated to the chromatin environment. In this context, our present work demonstrates that the pharmacological or genetic abrogation of HDAC6 in primary melanoma samples ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.12.012
更新日期:2016-05-01 00:00:00
abstract::Germ cell cancers (GCC) are the most frequent malignancy in young Caucasian males. GCC can consist of seminomas (SE) and non-seminomas (malignant NS: embryonal carcinoma (EC), yolk sac tumor (YS), choriocarcinoma (CH) and teratoma (TE)). Current serum-markers used for diagnosis and follow-up (AFP, hCG) are predominant...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.molonc.2013.08.002
更新日期:2013-12-01 00:00:00