Abstract:
:Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by EWS-ETS translocations and early metastasis to lung and bone. In this study, we investigated the role of the BRICHOS chaperone domain-containing endochondral bone protein chondromodulin I (CHM1) in ES pathogenesis. CHM1 is significantly overexpressed in ES, and chromosome immunoprecipitation (ChIP) data demonstrate CHM1 to be directly bound by an EWS-ETS translocation, EWS-FLI1. Using RNA interference, we observed that CHM1 promoted chondrogenic differentiation capacity of ES cells but decreased the expression of osteolytic genes such as HIF1A, IL6, JAG1, and VEGF. This was in line with the induction of the number of tartrate-resistant acid phosphatase (TRAP+ )-stained osteoclasts in an orthotopic model of local tumor growth after CHM1 knockdown, indicating that CHM1-mediated inhibition of osteomimicry might play a role in homing, colonization, and invasion into bone tissues. We further demonstrate that CHM1 enhanced the invasive potential of ES cells in vitro. This invasiveness was in part mediated via CHM1-regulated matrix metallopeptidase 9 expression and correlated with the observation that, in an xenograft mouse model, CHM1 was essential for the establishment of lung metastases. This finding is in line with the observed increase in CHM1 expression in patient specimens with ES lung metastases. Our results suggest that CHM1 seems to have pleiotropic functions in ES, which need to be further investigated, but appears to be essential for the invasive and metastatic capacities of ES.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
von Heyking K,Calzada-Wack J,Göllner S,Neff F,Schmidt O,Hensel T,Schirmer D,Fasan A,Esposito I,Müller-Tidow C,Sorensen PH,Burdach S,Richter GHSdoi
10.1002/1878-0261.12057subject
Has Abstractpub_date
2017-09-01 00:00:00pages
1288-1301issue
9eissn
1574-7891issn
1878-0261journal_volume
11pub_type
杂志文章abstract::Epigenetic changes can be defined as stable molecular alterations of a cellular phenotype such as the gene expression profile of a cell that are heritable during somatic cell divisions (and sometimes germ line transmissions) but do not involve changes of the DNA sequence itself. Epigenetic phenomena are mediated by se...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.04.002
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:The association between nuclear factor I/B (NFIB) gene and triple negative breast cancer has been previously suggested. METHODS:We investigated the relationship between NFIB mRNA and protein expression and molecular subtypes of breast cancer as well as the effect of NFIB silencing on the proliferation and a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.08.002
更新日期:2011-12-01 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::Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylatio...
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
abstract::The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tiss...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12487
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND:Breast cancer is a heterogeneous disease with different molecular subtypes that have varying responses to therapy. An ongoing challenge in breast cancer research is to distinguish high-risk patients from good prognosis patients. This is particularly difficult in the low-grade, ER-positive luminal A tumors, w...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.11.002
更新日期:2015-03-01 00:00:00
abstract::Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evalu...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.09.010
更新日期:2015-02-01 00:00:00
abstract::Targeted toxin-based therapeutics are hindered by poor intracellular uptake, limited stability and non-specific immune stimulation. To address these problems, ligand-targeted toxins in combination with low dose saponin mixtures have been adapted and tested in vivo in the past, however, undefined saponin raw mixtures a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2012.12.004
更新日期:2013-06-01 00:00:00
abstract::GPNMB is a melanoma-associated glycoprotein that is targeted by the CR011-vcMMAE antibody-drug conjugate (ADC). Previous studies have shown that CR011-vcMMAE induces the apoptosis of GPNMB-expressing tumor cells in vitro and tumor regression in xenograft models. This ADC is currently in clinical trials for melanoma. I...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2008.02.002
更新日期:2008-06-01 00:00:00
abstract::Breast cancer tissue overexpresses fucosylated glycans, such as sialyl-Lewis X/A (sLeX/A ), and α-1,3/4-fucosyltransferases (FUTs) in relation to increased disease progression and metastasis. These glycans in tumor circulating cells mediate binding to vascular E-selectin, initiating tumor extravasation. However, their...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12163
更新日期:2018-05-01 00:00:00
abstract::The elevated expression and activation of human telomerase reverse transcriptase (hTERT) is associated with the unlimited proliferation of cancer cells. However, the excise mechanism of hTERT regulation during carcinogenesis is not well understood. In this study, we discovered cleavage and polyadenylation specific fac...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.02.001
更新日期:2014-05-01 00:00:00
abstract::The pivotal role of LYRIC/AEG-1 in malignant transformation, tumourigenesis and chemo-resistance has previously been demonstrated in different cell types and sub-cellular compartments. The localisation of LYRIC/AEG-1 appears crucial to its function and is regulated by three lysine-rich nuclear localisation signal regi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.01.009
更新日期:2014-05-01 00:00:00
abstract::Breast cancers with BRCA1 germline mutation have a characteristic DNA copy number (CN) pattern. We developed a test that assigns CN profiles to be 'BRCA1-like' or 'non-BRCA1-like', which refers to resembling a BRCA1-mutated tumor or resembling a tumor without a BRCA1 mutation, respectively. Approximately one third of ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.03.002
更新日期:2015-08-01 00:00:00
abstract::Brain metastases are life-threatening complications of triple-negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo a...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12752
更新日期:2020-09-01 00:00:00
abstract::Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12-p11 and encodes a key DNA base excision...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.01.001
更新日期:2014-05-01 00:00:00
abstract::We have recently gained a remarkable understanding of the mutational landscape of head and neck squamous cell carcinoma (HNSCC). However, the nature of the dysregulated signaling networks contributing to HNSCC progression is still poorly defined. Here, we have focused on the role of the family of mitogen activated kin...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.10.003
更新日期:2014-02-01 00:00:00
abstract::Targeted therapies, including antibodies, are becoming increasingly important in cancer therapy. Important limitations, however, are that not every patient benefits from a specific antibody therapy and that responses could be short-lived due to acquired resistance. In addition, targeted therapies are quite expensive a...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.03.010
更新日期:2014-06-01 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::Bone morphogenetic proteins (BMPs) are a group of growth factors with dual functions in cancer development and progression. Recently, certain tumor-promoting roles have been identified for selected antagonists/inhibitors (BMPIs) of this developmental pathway. A recent focus on the implication of BMP in colorectal canc...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.04.004
更新日期:2014-10-01 00:00:00
abstract::Natural products remain a significant source of anticancer chemotherapeutics. The search for targeted drugs for cancer treatment includes consideration of natural products, which may provide new opportunities for antitumor cytotoxicity as single agents or in combination therapy. We examined the association of molecula...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12849
更新日期:2020-11-09 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::As treatment options for patients with incurable metastatic castration-resistant prostate cancer (mCRPC) are considerably limited, novel effective therapeutic options are needed. Checkpoint kinase 1 (CHK1) is a highly conserved protein kinase implicated in the DNA damage response (DDR) pathway that prevents the accumu...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12756
更新日期:2020-10-01 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::Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from larg...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.04.011
更新日期:2010-06-01 00:00:00
abstract::Periampullary adenocarcinomas can be of two histological subtypes, intestinal or pancreatobiliary. The latter is more frequent and aggressive, and characterized by a prominent desmoplastic stroma, which is tightly related to the biology of the cancer, including its poor response to chemotherapy. Whereas miRNAs are kno...
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::Prostate cancer (PCa) remains an important public health concern in Western countries. Metabolic syndrome (MeS) is a cluster of pathophysiological disorders with increasing prevalence in the general population that is a risk factor for PCa. Several studies have determined that a crosstalk between white adipose tissue ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12788
更新日期:2020-09-02 00:00:00
abstract::It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cr...
journal_title:Molecular oncology
pub_type: 临床试验,杂志文章
doi:10.1002/1878-0261.12025
更新日期:2017-02-01 00:00:00
abstract::The presence of circulating tumor cells (CTCs) in the blood of ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs with epithelial-mesenchymal-transition (EMT) or stem-like traits are supposed to be involved in metastatic progression and recurrence. Thus, investigating the tran...
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::ATR-CHEK1 signalling is critical for genomic stability. ATR-CHEK1 signalling may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. We investigated ATR, CHEK1 and phosphorylated CHEK1 (Ser345) protein (pCHEK1) levels in 1712 breast cancers. ATR and CHEK1 mRNA expression was e...
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
abstract::C13ORF18 is frequently hypermethylated in cervical cancer but not in normal cervix and might serve as a biomarker for the early detection of cervical cancer in scrapings. As hypermethylation is often observed for silenced tumor suppressor genes (TSGs), hypermethylated biomarker genes might exhibit tumor suppressive ac...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.02.017
更新日期:2013-06-01 00:00:00