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 activities upon re-expression. Epigenetic drugs are successfully exploited to reverse TSG silencing, but act genome-wide. Artificial Transcription Factors (ATFs) provide a gene-specific approach for re-expression of silenced genes. Here, we investigated the potential tumor suppressive role of C13ORF18 in cervical cancer by ATF-induced re-expression. Five zinc finger proteins were engineered to bind the C13ORF18 promoter and fused to a strong transcriptional activator. C13ORF18 expression could be induced in cervical cell lines: ranging from >40-fold in positive (C13ORF18-unmethylated) cells to >110-fold in negative (C13ORF18-methylated) cells. Re-activation of C13ORF18 resulted in significant cell growth inhibition and/or induction of apoptosis. Co-treatment of cell lines with ATFs and epigenetic drugs further enhanced the ATF-induced effects. Interestingly, re-activation of C13ORF18 led to partial demethylation of the C13ORF18 promoter and decreased repressive histone methylation. These data demonstrate the potency of ATFs to re-express and potentially demethylate hypermethylated silenced genes. Concluding, we show that C13ORF18 has a TSG function in cervical cancer and may serve as a therapeutic anti-cancer target. As the amount of epimutations in cancer exceeds the number of gene mutations, ATFs provide promising tools to validate hypermethylated marker genes as therapeutic targets.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
Huisman C,Wisman GB,Kazemier HG,van Vugt MA,van der Zee AG,Schuuring E,Rots MGdoi
10.1016/j.molonc.2013.02.017subject
Has Abstractpub_date
2013-06-01 00:00:00pages
669-79issue
3eissn
1574-7891issn
1878-0261pii
S1574-7891(13)00041-0journal_volume
7pub_type
杂志文章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 identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic op...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12433
更新日期:2019-02-01 00:00:00
abstract::Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer-related pathways. Because APE1 is essential for cell viability, generation of APE1-knockout cell lines and determining a comprehensive list of genes...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12138
更新日期:2017-12-01 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::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...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12889
更新日期:2020-12-19 00:00:00
abstract::C4.4A is a metastasis-associated molecule that functions appear to rely on associated alph6beta4 integrin. To corroborate the impact of the C4.4A-alpha6beta4 integrin association on metastasis formation, C4.4A was knocked-down in a highly metastatic rat pancreatic adenocarcinoma (ASML, ASML-C4.4Akd). Metastasis format...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.05.002
更新日期:2013-10-01 00:00:00
abstract::Our limited understanding of the biological impact of the whole spectrum of early breast lesions together with a lack of accurate molecular-based risk criteria for the diagnosis and assignment of prognostic significance to biopsy findings presents an important problem in the clinical management of patients harboring p...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.09.005
更新日期:2010-12-01 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::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::Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Dysregulation of long noncoding RNAs during the preliminary stages of breast carcinogenesis is poorly understood. In this study, we performed RNA sequencing to identify long noncoding RNA expression profiles associated ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12489
更新日期:2019-06-01 00:00:00
abstract::Histone methyltransferases (HMTs) catalyze the methylation of lysine and arginine residues on histone tails and non-histone targets. These important post-translational modifications are exquisitely regulated and affect chromatin compaction and transcriptional programs leading to diverse biological outcomes. There is a...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2016.09.003
更新日期:2016-12-01 00:00:00
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::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::Breast cancer (BrCa) metabolism is geared toward biomass synthesis and maintenance of reductive capacity. Changes in glucose and glutamine metabolism in BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa biology remains to be determined. We recently reported that adipocyte coculture alte...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12368
更新日期:2018-09-01 00:00:00
abstract::In order to secure high-quality cancer care for increasing numbers of cancer patients in the upcoming decades, the complete continuum of cancer research and cancer care needs a thorough overhaul, with more emphasis on prevention and early detection, and a greater focus on the development of innovative treatments that ...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12441
更新日期:2019-03-01 00:00:00
abstract::Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.07.010
更新日期:2016-11-01 00:00:00
abstract::The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown tha...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12636
更新日期:2020-03-01 00:00:00
abstract::CDC25 (cell division cycle 25) phosphatases are essential for cell cycle control under normal conditions and in response to DNA damage. They are represented by three isoforms, CDC25A, B and C, each of them being submitted to an alternative splicing mechanism. Alternative splicing of many genes is affected in response ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2012.06.003
更新日期:2012-10-01 00:00:00
abstract::The ability to predict responsiveness to drugs in individual patients is limited. We hypothesized that integrating molecular information from databases would yield predictions that could be experimentally tested to develop transcriptomic signatures for specific drugs. We analyzed lung adenocarcinoma patient data from ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12521
更新日期:2019-08-01 00:00:00
abstract::Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.007
更新日期:2016-05-01 00:00:00
abstract::Molecular characterization of cancers is important in dictating prognostic factors and directing therapy. Next-generation sequencing of plasma circulating tumor DNA (ctDNA) offers less invasive, more convenient collection, and a more real-time representation of a tumor and its molecular heterogeneity than tissue. Howe...
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
abstract::Endoplasmic reticulum (ER) stress is an adaptive response to various stress conditions and plays emerging roles in cancer. Activating transcription factor 6 (ATF6), one of the three major ER stress transducers, has been shown to contribute to chemoresistance by altering cancer cell survival. Cancerous inhibitor of pro...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12365
更新日期:2018-10-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT) is an important process in embryonic development, fibrosis, and cancer metastasis. During cancer progression, the activation of EMT permits cancer cells to acquire migratory, invasive, and stem-like properties. A growing body of evidence supports the critical link between EMT an...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1002/1878-0261.12096
更新日期:2017-07-01 00:00:00
abstract::Targeted therapy for patients with HER2-positive (HER2+) breast cancer has improved overall survival, but many patients still suffer relapse and death from the disease. Intratumor heterogeneity of both estrogen receptor (ER) and HER2 expression has been proposed to play a key role in treatment failure, but little work...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12375
更新日期:2018-11-01 00:00:00
abstract::Current hypotheses suggest that tumors originate from cells that carry out a process of "malignant reprogramming" driven by genetic and epigenetic alterations. Multiples studies reported the existence of stem-cell-like cells that acquire the ability to self-renew and are able to generate the bulk of more differentiate...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2012.10.006
更新日期:2012-12-01 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::Peritoneal dissemination is a major clinical obstacle in gastrointestinal cancer therapy, and it accounts for the majority of cancer-related mortality. Calreticulin (CRT) is over-expressed in gastric tumors and has been linked to poor prognosis. In this study, immunohistochemistry studies revealed that the up-regulati...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.009
更新日期:2015-04-01 00:00:00
abstract::Next-generation sequencing (NGS) has recently been rapidly adopted in the molecular diagnosis of cancer, but it still faces some obstacles. In this study, 665 lung adenocarcinoma samples (558 TKI-naive and 107 TKI-relapsed samples) were interrogated using NGS, and the challenges and possible solutions of subjecting ap...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12190
更新日期:2018-05-01 00:00:00
abstract::Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases, however, their role in tumor biology and as a drug target is not clear. In the present study, a stable neurotensin (NT) analog induced intracellular calcium release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer ce...
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
abstract::Recently, RNAs interacting with proteins have been implicated in playing an important role in the occurrence and progression of oesophageal squamous cell carcinoma (ESCC). In this study, we found that NELFA mRNA interacts with Rad17 through a novel noncoding mode in the nucleus and that the aberrant expression of USF2...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12619
更新日期:2020-03-01 00:00:00