Cell surface nucleolin is crucial in the activation of the CXCL12/CXCR4 signaling pathway

Yang, Xijia; Xu, Zuo-Feng; Li, Daotang; Cheng, Shaomei; Fan, Kang-Hsien; Liu, Chengjun; Li, Aiping; Zhang, Jing; Feng, Man

doi:10.1007/s13277-013-1044-0

Cited by 14 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD4 and CXCR4/CCR5, through co-ordinated interactions with heparan sulfate proteoglycans and cell-surface-expressed NCL [7] . NCL was found in cellular fractions containing the HIV genome, viral matrix and reverse transcriptase as well as in cross-linked complexes with CD4 and CXCR4/CCR5 at the cell membrane, supporting its potential role in viral entry [8] , [9] . Cell-surface NCL is markedly downregulated immediately after HIV entry into permissive cells as a consequence of its translocation into the cytoplasm [8] .…”

Section: Introductionmentioning

confidence: 80%

The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the host cell

Perrone

Butovskaya

Lago

et al. 2016

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 80%

The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the host cell

Perrone

Butovskaya

Lago

et al. 2016

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Several reports have shown that NCL inhibition by siRNAs or anti-NCL aptamers affects cell viability, proliferation, and migration (14,19,(37)(38)(39)(40)(41)(42)(43). To assess the effects of 4LB5 on cell viability and proliferation, we performed a dose-response (0.9-240 nM) experiment using the scFv on MDA-MB-231 triple-negative breast cancer (TNBC) cells at different time points (24,48, and 72 h).…”

Section: Significancementioning

confidence: 99%

Human anti-nucleolin recombinant immunoagent for cancer therapy

Palmieri

Richmond

Piovan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCLdependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immunebased NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers.is one of the most abundant nonribosomal proteins in the nucleolus (1), first identified in ribosomal RNA processing (2). Additional studies have demonstrated that NCL is a multifunctional nucleocytoplasmic protein, involved in ribosomal assembly, chromatin decondensation, transcription, nucleo-cytoplasmic import/export, and chromatin remodeling (3, 4). NCL is frequently up-regulated in cancer and in cancerassociated endothelial cells compared with normal tissues (5, 6), where it is also present on the cell surface (7,8). Altered NCL expression and localization results in oncogenic effects, such as stabilization of AKT, Bcl-2, Bcl-XL, and IL-2 mRNAs (9-11). Moreover, surface-NCL acts as a receptor for several oncogenic ligands (12-15) and viruses (16). Recently, we reported that NCL has a critical protumorigenic function regulating the biogenesis of selected microRNAs (miRNAs), a class of noncoding single-stranded RNAs 19-22 nt in length (17) that regulate gene expression at the posttranscriptional level by targeting mRNAs in a sequence-specific manner (18). In fact, NCL enhances the maturation of specific miRNAs (including miR-21, miR-221, and miR-222) causally involved in cancer pathogenesis and resistance to several antineoplastic treatments (19-23). Our findings demonstrated that NCL modulates the biogenesis of these miRNAs at the posttranscriptional level, enhancing their maturation from pri-to premiRNAs, identifying a novel NCL-dependent oncogenic mechanism (19).Because of its oncogenic role and specific expression on cancer cells surface, NCL represents an attractive target f...

show abstract

Cell surface nucleolin is crucial in the activation of the CXCL12/CXCR4 signaling pathway

Cited by 14 publications

References 26 publications

The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the host cell

The G-quadruplex-forming aptamer AS1411 potently inhibits HIV-1 attachment to the host cell

Cell Surface Nucleolin Facilitates Enterovirus 71 Binding and Infection

Human anti-nucleolin recombinant immunoagent for cancer therapy

Contact Info

Product

Resources

About