Overexpression of nucleolin and different expression sites both related to the prognosis of gastric cancer

Qiu, Wensheng; Zhou, Fang; Zhang, Qian; Sun, Xiaoxiao; Shi, Xiaoli; Liang, Ye; Wang, Xiumei; Lu, Yue

doi:10.1111/apm.12131

Cited by 67 publications

(78 citation statements)

References 20 publications

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“…As a result, we found that the nuclear, cytoplasmic and cytoplasmic membrane stainings of nucleolin were all detected in HCC tissues while only nuclear staining was found in nonneoplastic tissues, implying that the subcellular localization of nucleolin may change during the carcinogenesis of HCC. This change has been observed by Qiu et al in gastric cancer [12]. According to recent studies, nucleolin acts as an oncogene and enables normal cells to become malignant through its RNA binding activity [33].…”

Section: Discussionmentioning

confidence: 69%

“…More importantly, the aberrant expression of nucleolin has also been demonstrated to be closely correlated with tumor progression and prognosis in several cancer types. For example, Qiu et al [12] indicated that the high expression level of nucleolin was an independent prognostic marker for worse survival of patients with gastric cancer; Zhao et al [13] determined that nucleolin expression independently predicted for worse survival of patients with non small cell lung cancer; Grinstein et al [14] identified nucleolin as activator of human papillomavirus type 18 oncogene transcription in cervical cancer; High levels of nucleolin expression have also been shown to correlate with poor survival in patients with cutaneous melanoma and pediatric intracranial ependymoma [15,16]. In contrast, Peng et al [34] reported that high levels of nucleolar expression of nucleolin may be associated with better prognosis in patients with stage II pancreatic ductal adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

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Increased level of nucleolin confers to aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma after hepatectomy

Guo

Xiong

et al. 2014

Diagn Pathol

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BackgroundNucleolin, as a multifunctional protein, has been demonstrated to play an oncogenic role in human hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression pattern of nucleolin in HCC and determine its correlation with tumor progression and prognosis.MethodsNucleolin expression at both mRNA and protein levels in HCC and adjacent nonneoplastic tissues were respectively detected by quantitative real time polymerase chain reaction (Q-PCR), immunohistochemistry and western blotting.ResultsNucleolin expression, at both mRNA and protein levels, was significantly higher in HCC tissues than in the adjacent nonneoplastic tissues (both P < 0.001). In addition, the elevated nucleolin expression was markedly correlated with advanced tumor stage (P = 0.001), high tumor grade (P = 0.02) and serum AFP level (P = 0.008). Moreover, HCC patients with high nucleolin expression had shorter 5-year disease-free survival and shorter 5-year overall survival than those with low expression (both P < 0.001). Furthermore, the Cox proportional hazards model showed that nucleolin expression was an independent poor prognostic factor for both 5-year disease-free survival (hazards ratio [HR] = 3.696, 95% confidence interval [CI] = 1.662-8.138, P = 0.01) and 5-year overall survival (HR = 3.872, CI = 1.681-8.392, P = 0.01) in HCC.ConclusionThese results showed that the markedly and consistently increasing expression of nucleolin may be associated with aggressive characteristics of HCC, and implied that nucleolin expression may serve as a promising biochemical marker for predicting the clinical outcome of patients with this malignancy.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_175.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Increased level of nucleolin confers to aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma after hepatectomy

Guo

Xiong

et al. 2014

Diagn Pathol

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“…It controls the metabolism of DNA and RNA in the nucleolus (44,45), shuttles proteins into the nucleus (46), provides posttranscriptional regulation of strategic mRNAs in the cytoplasm (47,48), and serves as a ligand for proteins, such as midkine and the heparin-binding growth-associated molecule, on the cell surface (49). NCL is also involved in the proliferation of many types of cancer (34,(50)(51)(52) and serves as a prognosis marker and therapeutic target for cancer treatment (53)(54)(55). Furthermore, NCL also participates in the pathogenic mechanism and mediates the replication of several viruses and/or serves as a cell surface receptor for Escherichia coli O157 (56), Helicobacter pylori (57), RSV (28), adeno-associated virus type-2 (AAV-2) (58), coxsackie B virus (59), and HIV (29).…”

Section: Discussionmentioning

confidence: 99%

Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

Wang

Huang

et al. 2015

J Virol

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Because the pathogenesis of enterovirus 71 (EV71) remains mostly ambiguous, identifying the factors that mediate viral binding and entry to host cells is indispensable to ultimately uncover the mechanisms that underlie virus infection and pathogenesis. Despite the identification of several receptors/attachment molecules for EV71, the binding, entry, and infection mechanisms of EV71 remain unclear. Herein, we employed glycoproteomic approaches to identify human nucleolin as a novel binding receptor for EV71. Glycoproteins purified by lectin chromatography from the membrane extraction of human cells were treated with sialidase, followed by immunoprecipitation with EV71 particles. Among the 16 proteins identified by tandem mass spectrometry analysis, cell surface nucleolin attracted our attention. We found that EV71 interacted directly with nucleolin via the VP1 capsid protein and that an antinucleolin antibody reduced the binding of EV71 to human cells. In addition, the knockdown of cell surface nucleolin decreased EV71 binding, infection, and production in human cells. Furthermore, the expression of human nucleolin on the cell surface of a mouse cell line increased EV71 binding and conferred EV71 infection and production in the cells. These results strongly indicate that human nucleolin can mediate EV71 binding to and infection of cells. Our findings also demonstrate that the use of glycoproteomic approaches is a reliable methodology to discover novel receptors for pathogens. IMPORTANCEOutbreaks of EV71 have been reported in Asia-Pacific countries and have caused thousands of deaths in young children during the last 2 decades. The discovery of new EV71-interacting molecules to understand the infection mechanism has become an emergent issue. Hence, this study uses glycoproteomic approaches to comprehensively investigate the EV71-interacting glycoproteins. Several EV71-interacting glycoproteins are identified, and the role of cell surface nucleolin in mediating the attachment and entry of EV71 is characterized and validated. Our findings not only indicate a novel target for uncovering the EV71 infection mechanism and anti-EV71 drug discovery but also provide a new strategy for virus receptor identification.

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“…The level of NCL synthesis is correlated with the rate of cell doubling, its expression is thus greater in many tumor cells types [21,22]. NCL is a marker of several human cancer such as colorectal gastric, lung, cervical and breast carcinomas, melanoma and glioblastoma [23][24][25][26][27][28][29][30][31][32][33][34].…”

Section: Ncl: a Promising Target For Cancer Therapymentioning

confidence: 99%

Nanoparticles Functionalized with Ligands of Cell Surface Nucleolin for Cancer Therapy and Diagnosis

Destouches¹

2015

J Nanomed Nanotechnol

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Conventional cancer chemotherapies are often limited by their non-targeted nature and their inadequate delivery to the tumor affecting the normal tissues and leading to toxic adverse effects. In order to improve the anticancer efficacy and safety of these drugs, as well as the diagnosis capacity of imaging agents, nanoparticles drug delivery system has been developed combining ligands enabling tumor targeting at a cellular level and drug carrier capacity. Nucleolin (NCL) is a multifunctional protein that could shuttle from nucleolus to nucleoplasm, cytoplasm and cell surface. This ribonucleo protein over expressed at the cell surface of cancer cells is involved in many cancer processes supporting tumorigenesis such as cell proliferation and apoptosis. Additionally, NCL expression is enhanced in angiogenic vessels, enabling multi-targeting strategies toward the tumor microenvironment. In this context, several compounds targeting NCL, such as the aptamer AS1411, the peptide F3 and the multivalent pseudopeptide N6L, have been developed and investigated for cancer therapy. Due to their cancer cell targeting capacities, these compounds have been evaluated to mediate highly specific and effective nanoparticles for drug delivery to the tumor. In this report, we present a review of literature focusing on drug-loaded nanoparticles conjugated with these nucleolin ligands, strikingly emphasizing the success of such a strategy.

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Overexpression of nucleolin and different expression sites both related to the prognosis of gastric cancer

Cited by 67 publications

References 20 publications

Increased level of nucleolin confers to aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma after hepatectomy

Increased level of nucleolin confers to aggressive tumor progression and poor prognosis in patients with hepatocellular carcinoma after hepatectomy

Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

Nanoparticles Functionalized with Ligands of Cell Surface Nucleolin for Cancer Therapy and Diagnosis

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