Identification of Nucleolin as a Lipid-Raft-Dependent β1-Integrin-Interacting Protein in A375 Cell Migration

Bi, Jiajia; Wang, Ruifei; Zhang, Yue; Han, Xiaoqing; Ampah, Khamal Kwesi; Liu, Wenguang; Zeng, Xianlu

doi:10.1007/s10059-013-0149-z

Cited by 15 publications

(14 citation statements)

References 43 publications

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“…Indeed, cell shape is drastically affected when NCL expression is reduced 27 – 29 . Many studies have shown that the expression of NCL is required for cell migration or adhesion 34 – 37 . In most of these studies, NCL silencing using siRNA reduced cell migration and invasion.…”

Section: Resultsmentioning

confidence: 99%

Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin

Kumar¹,

Gomez

Chalabi-Dchar

et al. 2017

Sci Rep

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Nucleolin is an essential protein that plays important roles in the regulation of cell cycle and cell proliferation. Its expression is up regulated in many cancer cells but its molecular functions are not well characterized. Nucleolin is present in the nucleus where it regulates gene expression at the transcriptional and post-transcriptional levels. Using HeLa cells depleted in nucleolin we performed an mRNA and miRNA transcriptomics analysis to identify biological pathways involving nucleolin. Bioinformatic analysis strongly points to a role of nucleolin in lipid metabolism, and in many signaling pathways. Down regulation of nucleolin is associated with lower level of cholesterol while the amount of fatty acids is increased. This could be explained by the decreased and mis-localized expression of the transcription factor SREBP1 and the down-regulation of enzymes involved in the beta-oxidation and degradation of fatty acids. Functional classification of the miRNA-mRNA target genes revealed that deregulated miRNAs target genes involved in apoptosis, proliferation and signaling pathways. Several of these deregulated miRNAs have been shown to control lipid metabolism. This integrated transcriptomic analysis uncovers new unexpected roles for nucleolin in metabolic regulation and signaling pathways paving the way to better understand the global function of nucleolin within the cell.

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Section: Resultsmentioning

confidence: 99%

Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin

Kumar¹,

Gomez

Chalabi-Dchar

et al. 2017

Sci Rep

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“…Given that both integrin β1 and versican signaling have demonstrated dependence on lipid raft domains for their function 4, 16, 31, 32 , we also evaluated the effect of disrupting lipid rafts on the hyperalgesia induced by PGE 2 and CPA in the primed rat. The lipid raft disruptor methyl-β-cyclodextrin reversibly attenuated PGE 2 -, but not CPA-induced mechanical hyperalgesia in primed rats.…”

Section: Discussionmentioning

confidence: 99%

Plasma Membrane Mechanisms in a Preclinical Rat Model of Chronic Pain

Ferrari

Levine

2015

The Journal of Pain

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We have recently shown that the prolongation of prostaglandin E2 (PGE2) hyperalgesia in a preclinical model of chronic pain – hyperalgesic priming – is mediated by release of cAMP from IB4-positive nociceptors and its metabolism by ectonucleotidases to produce adenosine. The adenosine, in turn, acts in an autocrine mechanism at an A1 adenosine receptor whose downstream signaling mechanisms in the nociceptor are altered to produce nociceptor sensitization. We previously showed that antisense against an extracellular matrix (ECM) molecule, versican, which defines the population of nociceptors involved in hyperalgesic priming, eliminated the prolongation of PGE2 hyperalgesia. To further evaluate the mechanisms at the interface between the ECM and the nociceptor’s plasma membrane involved in hyperalgesia prolongation, we interrupted a plasma membrane molecule involved in versican signaling, integrin β1, with an antisense oligodeoxynucleotide. Integrin β1 antisense eliminated mechanical hyperalgesia induced by an adenosine A1 receptor agonist, cyclopentyladenosine (CPA), in the primed rat. We also disrupted a molecular complex of signaling molecules that contains integrin β1, lipid rafts, with methyl-β-cyclodextrin, which attenuated the prolongation without affecting the acute phase of PGE2 hyperalgesia, while having no effect on CPA hyperalgesia. Our findings help to define the plasma membrane mechanisms involved in a preclinical model of chronic pain.

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“…In interphase cells, regulation of microtubule dynamics is essential for numerous processes including cell architecture [ 34 ], intracellular trafficking and cell adhesion [ 35 , 36 ], cell polarization [ 37 ] and migration [ 38 ]. Interestingly, nucleolin has been associated to microtubule dependent intracellular trafficking [ 13 , 39 ] and has been implicated in cell adhesion and migration [ 9 , 12 , 40 ] It would be interesting to reevaluate the function of nucleolin in these processes by taking into account the involvement of nucleolin microtubule stabilization described herein. Indeed, in this report we show that nucleolin expression levels affect the different subpopulations of microtubules at the center and at the periphery of the cells ( Fig 4 ), arguing for a global role of nucleolin on microtubule dynamics independently of their subcellular localization.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, several functions of nucleolin have been described in the nucleoplasm, cytoplasm and at the cell membrane. Through its numerous sub cellular localizations and functions, nucleolin has been involved in the initiation and progression of lots of cancers [ 8 ] and more specifically in processes that could involve microtubules dynamics like cell adhesion and migration [ 9 – 12 ] as well as intracellular trafficking [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of Nucleolin Affects Microtubule Dynamics

Gaume¹,

Place²,

Delage³

et al. 2016

PLoS ONE

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Nucleolin is present in diverse cellular compartments and is involved in a variety of cellular processes from nucleolar structure and function to intracellular trafficking, cell adhesion and migration. Recently, nucleolin has been localized at the mature centriole where it is involved in microtubule nucleation and anchoring. Although this new function of nucleolin linked to microtubule regulation has been identified, the global effects of nucleolin on microtubule dynamics have not been addressed yet. In the present study, we analyzed the roles of nucleolin protein levels on global microtubule dynamics by tracking the EB3 microtubule plus end binding protein in live cells. We have found that during microtubule growth phases, nucleolin affects both the speed and life time of polymerization and by analyzing catastrophe events, we showed that nucleolin reduces catastrophe frequency. This new property of nucleolin was then confirmed in a cold induced microtubule depolymerization experiment in which we have found that cold resistant microtubules were totally destabilized in nucleolin depleted cells. Altogether, our data demonstrate a new function of nucleolin on microtubule stabilization, thus bringing novel insights into understanding the multifunctional properties of nucleolin in healthy and cancer cells.

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Identification of Nucleolin as a Lipid-Raft-Dependent β1-Integrin-Interacting Protein in A375 Cell Migration

Cited by 15 publications

References 43 publications

Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin

Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin

Plasma Membrane Mechanisms in a Preclinical Rat Model of Chronic Pain

Expression of Nucleolin Affects Microtubule Dynamics

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