The Role of Nucleophosmin in Cell Functioning and Tumor Progression

Понкратова, Д. А.; Лушникова, А. А.

doi:10.1134/s2079086420040064

Cited by 3 publications

(5 citation statements)

References 107 publications

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“…According our data, BC cell apoptosis was accompanied by an increase of the frequency of double-stranded DNA breaks, degradation of chromatin and mitotic spindle, migration of NPM from the nucleus and activation of the p53 suppressor protein. 3,5 Analysis by molecular docking between CP and NPM, CP and NCL, CP and pGP protein; CP-Dox and pGP revealed significantly more energetically advantageous binding (scores modulo) between CP and NCL. In particular, the binding of pGP to CP KK-13-Dox is characterized by a maximum estimated function = -6,202.…”

Section: Resultsmentioning

confidence: 99%

“…Its proposed mechanism is a binding of cell surface NCL by cationic peptides, dislocation NPM molecular from the nucleus to the cytoplasm, the release of suppressor p53 and subsequent apoptosis. 3 It would allow to develop fundamental algorithm for the applications of some cationic peptides as anticancer agents with high selective toxicity to tumors, regardless of cancer origin and localization. The expected results justify the strategy for obtaining targeted drugs on the basis of cationic peptides taking into account the expression of their cellular targets, and a certain tactics for clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…The proposed mechanism includes a binding of cell surface NCL molecula by cationic peptides, dislocation nucleophosmin from the nucleus to the cytoplasm, the release of suppressor p53 and subsequent apoptosis. 3 These results justify the strategy for obtaining anticancer drugs on the basis of cationic peptides for overcoming acquired drug resistance.…”

Section: Introductionmentioning

confidence: 90%

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Novel approaches for overcoming of tumor drug resistance by polyvalent cationic peptides

Лушникова¹,

Onyan²,

Kovtun³

et al. 2023

JCPCR

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Background: Acquired resistance to various drugs is a key challenge for anticancer therapy. Earlier we have revealed a selective apoptosis of tumor cells induced by polyvalent cationic peptides (CPs) both in vitro and in vivo by inactivation their cell targets -multifunctional chaperone proteins nucleolin (NCL) and nucleophosmin (NPM). Here we applied Arg/ Lys-enriched CPs as well as CPs, conjugated with Doxorubicin (Dox) to induce cell death by nucleolar stress mechanisms both in Dox-sensitive breast cancer (BC) cells and in Dox-resistant ones. Molecular interactions between CP as ligand and cellular targets using computer modeling by docking have been done. Then, CP potential for anticancer therapy of various malignant tumors is discussed.Objective: An analysis of cell survival in breast cancer (BC) sublines that are sensitive or resistant to Doxorubicin (Dox) by cationic peptides (CPs) and conjugate CP +Dox. Results:The data indicate that Arg/Lys enriched CPs might be perspective agents for inducing BC cell apoptosis and for transport Dox or other drugs in tumor cells to overcome drug resistance. Conclusion:Molecular docking is effective tool for modeling and evaluating of interactions and competitive binding of CPs to their cellular targets. This approach is also useful for design novel peptides with high anticancer properties and low toxicity for patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Novel approaches for overcoming of tumor drug resistance by polyvalent cationic peptides

Лушникова¹,

Onyan²,

Kovtun³

et al. 2023

JCPCR

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show abstract

“…NPM1 is involved in tumor progression, especially with the role in ribosome biogenesis that is increased in cancer cells [ 45 , 46 ]. It promotes the nuclear export of 40S and 60S ribosomal subunits into the cytoplasm to increase the number of 80S ribosomes, and then leading to increased cell proliferation [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Puf-A promotes cancer progression by interacting with nucleophosmin in nucleolus

et al. 2022

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Previously, we identified Puf-A as a novel member of Puf-family RNA-binding proteins; however, its biological functions remain obscure. Analysis of tumor samples of non-small cell lung cancer (NSCLC) showed that high Puf-A expression correlated with high histology grade and abnormal p53 status. Kaplan–Meier curve for overall survival revealed high expression of Puf-A to predict poor prognosis in stage I NSCLC. Among patients with colorectal cancer, high Puf-A expression also showed an adverse impact on overall survival. In lung cancer cell lines, downregulation of p53 increased Puf-A expression, and upregulation of p53 dampened its expression. However, luciferase reporter assays indicated that PUF-A locus harbored the p53-response element, but regulated Puf-A transcription indirectly. In vivo suppression of p53 in CCSP-rtTA/TetO-Cre/LSL-KrasG12D/p53flox/flox conditional mutant mice accelerated the progression of the KrasG12D-driven lung cancer, along with enhanced expression of Puf-A. Importantly, intranasal delivery of shPuf-A to the inducible KrasG12D/p53flox/flox mice suppressed tumor progression. Puf-A silencing led to marked decreases in the 80S ribosomes, along with decrease in S6 and L5 in the cytoplasm and accumulation in the nucleolus. Based on immunofluorescence staining and immunoprecipitation studies, Puf-A interacted with NPM1 in nucleolus. Puf-A silencing resulted in NPM1 translocation from nucleolus to nucleoplasm and this disruption of NPM1 localization was reversed by a rescue experiment. Mechanistically, Puf-A silencing altered NPM1 localization, leading to the retention of ribosomal proteins in nucleolus and diminished ribosome biogenesis, followed by cell-cycle arrest/cell death. Puf-A is a potential theranostic target for cancer therapy and an important player in cancer progression.

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“…As a well‐known nucleolar phosphoprotein, NPM1 has been found to be strongly correlated with cell proliferation and cancer pathogenesis. This gene has oncogenic and tumour‐suppressing functions through the frequent overexpression or genetic modification 25 , 26 , 27 , 28 . The mutation of NPM1 has been proved to be related to leukaemia and lymphoma 29 , 30 .…”

Section: Introductionmentioning

confidence: 99%

KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM

Zheng

Deng

et al. 2021

J Cellular Molecular Medi

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Renal cell carcinoma (RCC) is one the most common cancers worldwide, accounting for 2% of global cancer deaths and more than 90% of cancer diagnoses in the kidney 1 . More than 14,770 deaths were estimated in the United States at 2019 2 . Three major subtypes, clear cell RCC 3 , papillary RCC 4 and chromophobe RCC 5 , and a rare subtypes 6 unable to fit any subtype diagnostic criteria, were present in clinical patients 7 . Among these subtypes of RCC, clear cell RCC (ccRCC), also known as kidney renal clear cell carcinoma (KIRC), is the most common one, causing approximately 13,000 deaths in China at 2014 8 . As one of the well-known cancers with resistant to radiotherapy and chemotherapy 1 , ccRCC causes less than 20% 2-year survival rate of patients, which requires well-defined diagnostic biomarkers to facilitate early detection and risk stratification. Surgery is the primary treatment choice for localized renal cancer. Localized RCC can be treated with partial or radical nephrectomy ablation or active surveillance 9-11 , yet up to 30% of these patients develop metastases eventually nonetheless 12 . There are currently no efficient immunotherapy and molecular targeted drugs because of the overt complexity of intratumour and intertumour heterogeneity for clinical outcomes observed 4,[13][14][15] . Therefore, it is imperative to reveal the underlying molecular mechanisms and to identify molecular biomarkers of ccRCC for therapeutic targets.Nuclear transporters play a crucial role in regulating the pathological development of cancers. Karyopherin α2 (KPNA2, also known as importin α1) belongs to 7 members of the karyopherin α (also called importin α) protein family, which plays a major role in

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The Role of Nucleophosmin in Cell Functioning and Tumor Progression

Cited by 3 publications

References 107 publications

Novel approaches for overcoming of tumor drug resistance by polyvalent cationic peptides

Novel approaches for overcoming of tumor drug resistance by polyvalent cationic peptides

Puf-A promotes cancer progression by interacting with nucleophosmin in nucleolus

KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM

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