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• W2037991649 endingPage "e15787" @default.
• W2037991649 startingPage "e15787" @default.
• W2037991649 abstract "Background Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in tumorigenesis and angiogenesis. Emerging evidence suggests that the cell-surface expressed nucleolin is a strategic target for an effective and nontoxic cancer therapy. Methodology/Principal Findings By monitoring the expression of nucleolin mRNA, and by measuring the level of nucleolin protein recovered from the surface and nucleus of cells, here we show that the presence of nucleolin at the cell surface is dependent on the constant induction of nucleolin mRNA. Indeed, inhibitors of RNA transcription or translation block expression of surface nucleolin while no apparent effect is observed on the level of nucleolin in the nucleus. The estimated half-life of surface nucleolin is less than one hour, whereas that of nuclear nucleolin is more than 8 hours. Nucleolin mRNA induction is reduced markedly in normal fibroblasts that reach confluence, while it occurs continuously even in post-confluent epithelial tumor cells consistent with their capacity to proliferate without contact inhibition. Interestingly, cold and heat shock induce nucleolin mRNA concomitantly to enhanced mRNA expression of the heat shock protein 70, thus suggesting that surface nucleolin induction also occurs in response to an environmental insult. At the cell surface, one of the main functions of nucleolin is to shuttle specific extracellular ligands by an active transport mechanism, which we show here to be calcium dependent. Conclusion/Significance Our results demonstrate that the expression of surface nucleolin is an early metabolic event coupled with tumor cell proliferation and stress response. The fact that surface nucleolin is constantly and abundantly expressed on the surface of tumor cells, makes them a preferential target for the inhibitory action of anticancer agents that target surface nucleolin." @default.
• W2037991649 created "2016-06-24" @default.
• W2037991649 creator A5000206901 @default.
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• W2037991649 creator A5056516116 @default.
• W2037991649 creator A5069405280 @default.
• W2037991649 date "2010-12-23" @default.
• W2037991649 modified "2023-10-18" @default.
• W2037991649 title "Surface Expressed Nucleolin Is Constantly Induced in Tumor Cells to Mediate Calcium-Dependent Ligand Internalization" @default.
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• W2037991649 doi "https://doi.org/10.1371/journal.pone.0015787" @default.
• W2037991649 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3009748" @default.
• W2037991649 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21203423" @default.
• W2037991649 hasPublicationYear "2010" @default.
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