The roles of nucleolin subcellular localization in cancer

Berger, Caroline M.; Gaume, Xavier; Bouvet, Philippe

doi:10.1016/j.biochi.2015.03.023

Cited by 199 publications

(251 citation statements)

References 103 publications

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“…Conversely, other studies have found NPM1 overexpression to be a common feature of solid tumors from numerous different tissues, demonstrating that NPM1 can act as either a tumor suppressor or an oncogene depending on the cell and/or tissue type affected (Colombo et al 2011). Tumor suppressor activities have not been reported for NCL so far; D r a f t 33 however, overexpression of NCL has been linked to the development, progression and malignancy of a wide variety of solid and hematological tumors, identifying this protein as a major oncogene in numerous cellular systems (Berger et al 2015). This diversity of pathogenic roles for NPM1 and NCL, and their contribution to numerous essential proliferative pathways, make these two proteins exciting future targets for the development of multi-active chemotherapeutic agents (Poletto et al 2015;Sekhar et al 2011).…”

Section: Nucleoplasmic Translocation: a Mechanism Of Recruitment Or mentioning

confidence: 99%

“…uS3) has been reported to act as an apurinic/apyrimidinic endonuclease in both nuclear and mitochondrial base excision repair (Kim et al 2013), while nucleostemin/GNL3 has been implicated in the recruitment of RAD51 to stalled replication forks Meng et al 2013), and Nol12 has D r a f t 5 been identified as an important protective factor against oxidative DNA damage (Scott et al 2016). Most strikingly, two proteins -nucleophosmin (NPM1) and nucleolin (NCL) -are required for optimal activity of multiple independent DNA repair pathways, and their dysregulation has been reported in numerous cancers, in particular leukemias and other myeloproliferative disorders (Berger et al 2015;Colombo et al 2011;Federici et al 2013).…”

Section: Introductionmentioning

confidence: 99%

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Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair

Scott

Oeffinger

2016

Biochem. Cell Biol.

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The nucleolus represents a highly multifunctional intranuclear organelle in which, in addition to the canonical ribosome assembly, numerous processes such as transcription, DNA repair and replication, the cell cycle and apoptosis are coordinated. The nucleolus is further a key hub in the sensing of cellular stress and undergoes major structural and compositional changes in response to cellular perturbations.Numerous nucleolar proteins have been identified that, upon nucleolar stress sensing, deploy additional, non-ribosomal roles in the regulation of varied cell processes including cell cycle arrest, arrest of DNA replication, induction of DNA repair, and apoptosis, among others. The highly abundant proteins nucleophosmin (NPM1) and nucleolin (NCL) are two such factors that transit to the nucleoplasm in response to stress, and participate directly in the repair of numerous different DNA damages. This review discusses the contributions made by NCL and/or NPM1 to the different DNA repair pathways employed by mammalian cells to repair DNA insults, and examines the implications of such activities for the regulation, pathogenesis and therapeutic targeting of NPM1 and NCL.

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Section: Nucleoplasmic Translocation: a Mechanism Of Recruitment Or mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair

Scott

Oeffinger

2016

Biochem. Cell Biol.

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“…Nucleolin is highly expressed in several types of cancer (4), and is a cancer-specific target, being localized at the cell surface of tumor cells and activated endothelial cells (EC; refs. 5-7).…”

Section: Introductionmentioning

confidence: 99%

“…5-7). Nucleolar nucleolin principally regulates rRNA transcription and ribogenesis whereas cell surface nucleolin acts as a low-affinity receptor for specific ligands (4). Moreover, nucleolin stabilizes the mRNA of antiapoptotic proteins (8).…”

Section: Introductionmentioning

confidence: 99%

Nucleolin Targeting Impairs the Progression of Pancreatic Cancer and Promotes the Normalization of Tumor Vasculature

et al. 2016

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Pancreatic cancer is a highly aggressive tumor, mostly resistant to the standard treatments. Nucleolin is overexpressed in cancers and its inhibition impairs tumor growth. Herein, we showed that nucleolin was overexpressed in human specimens of pancreatic ductal adenocarcinoma (PDAC) and that the overall survival significantly increased in patients with low levels of nucleolin. The nucleolin antagonist N6L strongly impaired the growth of primary tumors and liver metastasis in an orthotopic mouse model of PDAC (mPDAC). Similar antitumor effect of N6L has been observed in a highly angiogenic mouse model of pancreatic neuroendocrine tumor RIP-Tag2. N6L significantly inhibited both human and mouse pancreatic cell proliferation and invasion. Notably, the analysis of tumor vasculature revealed a strong increase of pericyte coverage and vessel perfusion both in mPDAC and RIP-Tag2 tumors, in parallel to an inhibition of tumor hypoxia. Nucleolin inhibition directly affected endothelial cell (EC) activation and changed a proangiogenic signature. Among the vascular activators, nucleolin inhibition significantly decreased angiopoietin-2 (Ang-2) secretion and expression in ECs, in the tumor and in the plasma of mPDAC mice. As a consequence of the observed N6L-induced tumor vessel normalization, pre-treatment with N6L efficiently improved chemotherapeutic drug delivery and increased the antitumor properties of gemcitabine in PDAC mice. In conclusion, nucleolin inhibition is a new anti-pancreatic cancer therapeutic strategy that dually blocks tumor progression and normalizes tumor vasculature, improving the delivery and efficacy of chemotherapeutic drugs. Moreover, we unveiled Ang-2 as a potential target and suitable response biomarker for N6L treatment in pancreatic cancer. Cancer Res; 76(24);

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“…NCL is over-expressed on the cell surface of many cancer cells and accumulating evidences validated cell surface nucleolin as a very promising target in the treatment of cancer. These studies have been commented in recent reviews that summarize publications and patents related to the use of NCL ligands in cancer therapies [10][11][12].…”

Section: Introductionmentioning

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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The roles of nucleolin subcellular localization in cancer

Cited by 199 publications

References 103 publications

Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair

Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair

Nucleolin Targeting Impairs the Progression of Pancreatic Cancer and Promotes the Normalization of Tumor Vasculature

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

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