Abstract:
BACKGROUND:Fibroblast growth factors FGF-1 and FGF-2 are often upregulated in tumors, but tightly bound to heparan sulphate proteoglycans of the extracellular matrix (ECM). One mechanism of their bioactivation relies on the FGF-binding protein (FGF-BP) which, upon reversible binding to FGF-1 or -2, leads to their release from the ECM. FGF-BP increases tumorigenicity and is highly expressed in tumors like colon carcinoma. In this paper, we analyse cellular and molecular consequences of RNAi-mediated FGF-BP knockdown in colon carcinoma, and explore the therapeutic effects of the nanoparticle-mediated delivery of small interfering RNAs (siRNAs) for FGF-BP targeting. RESULTS:Employing stable RNAi cells, we establish a dose-dependence of cell proliferation on FGF-BP expression levels. Decreased proliferation is mirrored by alterations in cell cycle distribution and upregulation of p21, which is relevant for mediating FGF-BP effects. While inhibition of proliferation is mainly associated with reduced Akt and increased GSK3β activation, antibody array-based analyses also reveal other alterations in MAPK signalling. Additionally, we demonstrate induction of apoptosis, mediated through caspase-3/7 activation, and alterations in redox status upon FGF-BP knockdown. These effects are based on the upregulation of Bad, Bax and HIF-1α, and the downregulation of catalase. In a therapeutic FGF-BP knockdown approach based on RNAi, we employ polymer-based nanoparticles for the in vivo delivery of siRNAs into established wildtype colon carcinoma xenografts. We show that the systemic treatment of mice leads to the inhibition of tumor growth based on FGF-BP knockdown. CONCLUSIONS:FGF-BP is integrated in a complex network of cytoprotective effects, and represents a promising therapeutic target for RNAi-based knockdown approaches.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Schulze D,Plohmann P,Höbel S,Aigner Adoi
10.1186/1476-4598-10-144subject
Has Abstractpub_date
2011-11-23 00:00:00pages
144issn
1476-4598pii
1476-4598-10-144journal_volume
10pub_type
杂志文章相关文献
Molecular Cancer文献大全abstract::Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0777-1
更新日期:2018-02-19 00:00:00
abstract:BACKGROUND:Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apop...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-10
更新日期:2010-01-20 00:00:00
abstract:BACKGROUND:Aberrant accumulation of beta-catenin plays an important role in a variety of human neoplasms. We recently reported accumulation of beta-catenin in parathyroid adenomas from patients with primary hyperparathyroidism (pHPT). In CTNNB1 exon 3, we detected a stabilizing mutation (S37A) in 3 out of 20 analyzed a...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-53
更新日期:2008-06-09 00:00:00
abstract:BACKGROUND:RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-017-0683-y
更新日期:2017-07-28 00:00:00
abstract:BACKGROUND:Cancer is the result of a multistep process of genomic alterations, including mutations in key regulatory proteins that result in loss of balanced gene expression and subsequent malignant transformation. Throughout the various stages of colorectal carcinoma (CRC), complex genetic alterations occur, of which ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-21
更新日期:2014-02-04 00:00:00
abstract::Exosomes have emerged as a novel approach for the treatment and diagnosis of cancer after RNA content was discovered in exosomes in 2007. As important meditators of intercellular communication, exosomes have become a strong focus of investigation for researchers in the past decade, as witnessed through the exponential...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0823-z
更新日期:2018-03-20 00:00:00
abstract:BACKGROUND:MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian tumors. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-118
更新日期:2010-05-24 00:00:00
abstract:BACKGROUND:Although both circular RNAs (circRNAs) and autophagy are associated with the function of breast cancer (BC), whether circRNAs regulate BC progression via autophagy remains unknown. In this study, we aim to explore the regulatory mechanisms and the clinical significance of autophagy-associated circRNAs in BC....
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-020-01152-2
更新日期:2020-03-25 00:00:00
abstract:BACKGROUND:In recent years, circular RNAs (circRNAs), a new star of non-coding RNA, have been emerged as vital regulators and gained much attention for involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, regulatory role, clinical significance and underlying mechanis...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-018-0933-7
更新日期:2019-01-08 00:00:00
abstract:BACKGROUND:The epithelial-to-mesenchymal transition (EMT) process results in a loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. Recently, the enzyme SIRT1 has been implicated in a variety of physiological processes; however, its role in regulating oral can...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-254
更新日期:2014-11-26 00:00:00
abstract::Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolen...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-016-0523-5
更新日期:2016-05-18 00:00:00
abstract:BACKGROUND:Truncated dopamine and cyclic-AMP-regulated phosphoprotein (t-DARPP) is frequently overexpressed in gastrointestinal malignancies. In this study, we examined the role of t-DARPP in regulating β-catenin. RESULTS:The pTopFlash construct that contains multiple TCF/LEF-binding sites was used as a measure of β-c...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-32
更新日期:2011-03-29 00:00:00
abstract::Mutations in polymerase ε (POLE) confer favorable prognosis and outcomes in various cancer types, but their role in non-small cell lung cancer (NSCLC) is unknown. Utilizing the data of 513 patients with adenocarcinoma (LUAD) and 497 patients with squamous cell carcinoma (LUSC) from The Cancer Genome Atlas (TCGA) cohor...
journal_title:Molecular cancer
pub_type: 信件
doi:10.1186/s12943-018-0832-y
更新日期:2018-04-12 00:00:00
abstract:BACKGROUND:Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but t...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0641-8
更新日期:2017-03-29 00:00:00
abstract::Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects t...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0913-y
更新日期:2018-11-26 00:00:00
abstract:BACKGROUND:Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been linked with proliferation, survival, invasion and angiogenesis of a variety of human cancer cells, including hepatocellular carcinoma (HCC). Thus, novel agents that can suppress STAT3 activation have potential for ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-66
更新日期:2014-03-21 00:00:00
abstract:INTRODUCTION:Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cel...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-1-4
更新日期:2002-10-04 00:00:00
abstract:BACKGROUND:Sharing the common neuroectodermal origin, melanoma and neuroblastoma are tumors widely diffused among adult and children, respectively. Clinical prognosis of aggressive neuroectodermal cancers remains dismal, therefore the search for novel therapies against such tumors is warranted. Curcumin is a phytochemi...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-137
更新日期:2010-06-03 00:00:00
abstract:BACKGROUND:Targeted therapies have improved therapeutic options of treating renal cell carcinoma (RCC). However, drug response is temporary due to resistance development. METHODS:Functional and molecular changes in RCC Caki-1 cells, after acquired resistance to the mammalian target of rapamycin (mTOR)-inhibitor everol...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-152
更新日期:2014-06-16 00:00:00
abstract:BACKGROUND:Abnormal amplification/expression of HER-2/neu oncogene has been causally linked with tumorigenesis and metastasis in breast cancer and associated with shortened overall survival of patients. Recently, heat shock protein 27 (Hsp27) was reported to be highly expressed in HER-2/neu positive tumors and cell lin...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-6-52
更新日期:2007-08-14 00:00:00
abstract::A vast array of tumor-derived genetic, proteomic and cellular components are constantly released into the circulation of cancer patients. These molecules including circulating tumor DNA and RNA, proteins, tumor and immune cells are emerging as convenient and accurate liquid biomarkers of cancer. Circulating cancer bio...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-018-0757-5
更新日期:2018-01-17 00:00:00
abstract:BACKGROUND:CD95 is a death receptor controlling not only apoptotic pathways but also activating mechanisms promoting tumor growth. During the acquisition of chemoresistance to oxaliplatin there is a progressive loss of CD95 expression in colon cancer cells and a decreased ability of this receptor to induce cell death. ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-161
更新日期:2010-06-23 00:00:00
abstract:BACKGROUND:Deregulated circular RNAs (circRNAs) are associated with the development of cancer and therapy resistance. However, functional research of circRNAs mostly focus on potential miRNA or protein binding and more potential regulation of circRNA on host gene DNA in cancers are yet to be inspected. METHOD:We perfo...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-020-01246-x
更新日期:2020-08-24 00:00:00
abstract::Since the publication of this work [1] and in response to a recent query that was brought to our attention in relation to the Western Blot in Figure 1(C) for NP2, protein lysates prepared around the same time as those presented in the manuscript in question, were run by SDS-PAGE under similar experimental conditions a...
journal_title:Molecular cancer
pub_type: 已发布勘误
doi:10.1186/s12943-020-1142-8
更新日期:2020-01-27 00:00:00
abstract::Infection with Human papillomaviruses (HPVs) leads to the development of a wide-range of cancers, accounting for 5% of all human cancers. A prominent example is cervical cancer, one of the leading causes of cancer death in women worldwide. It has been well established that tumor development and progression induced by ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-015-0361-x
更新日期:2015-04-17 00:00:00
abstract:BACKGROUND:The dioxin (AhR) receptor can have oncogenic or tumor suppressor activities depending on the phenotype of the target cell. We have shown that AhR knockdown promotes melanoma primary tumorigenesis and lung metastasis in the mouse and that human metastatic melanomas had reduced AhR levels with respect to benig...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0419-9
更新日期:2015-08-05 00:00:00
abstract:BACKGROUND:In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinic...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-113
更新日期:2011-09-14 00:00:00
abstract:BACKGROUND:In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an ad...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-133
更新日期:2011-11-01 00:00:00
abstract::The correlation between epigenetic aberrations and disease underscores the importance of epigenetic mechanisms. Here, we review recent findings regarding chromatin modifications and their relevance to cancer. ...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-5-60
更新日期:2006-11-08 00:00:00
abstract:BACKGROUND:Though esophageal cancer is three to four times more common among males than females worldwide, this type of cancer still ranks in the top incidence among women, even more than the female specific cancer types. The occurrence is currently attributed to extrinsic factors, including tobacco use and alcohol con...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-019-0949-7
更新日期:2019-02-08 00:00:00