NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma

Zhou, Yangfan; Fang, Yuan; Zhou, Junjie; Liu, Yulian; Wu, Shusheng; Xu, Bin

doi:10.3389/fgene.2021.771253

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…Both the shRNA and the NSC348884 method abolished the lethal AML phenotype, caused apoptosis, and sensitized AML cells to tretinoin and cytarabine [ 85 ]. Moreover, another study reports that NSC348884 can induce apoptosis in Ewing sarcoma cancer [ 86 ].…”

Section: Resultsmentioning

confidence: 99%

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Lee,

Bao

2024

IJMS

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Histone chaperones are integral to chromatin dynamics, facilitating the assembly and disassembly of nucleosomes, thereby playing a crucial role in regulating gene expression and maintaining genomic stability. Moreover, they prevent aberrant histone interactions prior to chromatin assembly. Disruption in histone chaperone function may result in genomic instability, which is implicated in pathogenesis. This review aims to elucidate the role of histone chaperones in cancer pathologies and explore their potential as therapeutic targets. Histone chaperones have been found to be dysregulated in various cancers, with alterations in expression levels, mutations, or aberrant interactions leading to tumorigenesis and cancer progression. In addition, this review intends to highlight the molecular mechanisms of interactions between histone chaperones and oncogenic factors, underscoring their roles in cancer cell survival and proliferation. The dysregulation of histone chaperones is significantly correlated with cancer development, establishing them as active contributors to cancer pathology and viable targets for therapeutic intervention. This review advocates for continued research into histone chaperone-targeted therapies, which hold potential for precision medicine in oncology. Future advancements in understanding chaperone functions and interactions are anticipated to lead to novel cancer treatments, enhancing patient care and outcomes.

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Section: Resultsmentioning

confidence: 99%

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Lee,

Bao

2024

IJMS

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“…NPM1 has been reported to be upregulated in various human cancers, including breast cancer, colorectal cancer, lung cancer, and ES, which promotes cell proliferation and apoptosis resistance [ 38 – 41 ]. Zhou et al demonstrated that NPM1 decreases ES cell apoptosis, consistent with our study [ 41 ]. We are the first to report the inhibitory effect of NPM1 on ferroptosis in ES.…”

Section: Discussionmentioning

confidence: 99%

AURKA inhibition induces Ewing’s sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis

Chen,

Hu,

Xiong

et al. 2024

Cell Death Dis

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Ewing’s sarcoma (ES) is a rare and highly aggressive malignant tumor arising from bone and soft tissue. Suffering from intractable or recurrent diseases, the patients’ therapy options are very limited. It is extremely urgent to identify novel potential therapeutic targets for ES and put them into use in clinical settings. In the present study, high-throughput screening of a small molecular pharmacy library was performed. The killing effect of the Aurora kinase A (AURKA) inhibitor TCS7010 in ES cells was identified, and AURKA was selected as the research object for further study. Disparate suppressants were adopted to study the cell death manner of TCS7010. TCS7010 and RNA silencing were used to evaluate the functions of AURKA in the apoptosis and ferroptosis of ES cells. Co-immunoprecipitation assay was used to investigate the correlation of AURKA and nucleophosmin1 (NPM1) in ES. Nude-mice transplanted tumor model was used for investigating the role of AURKA in ES in vivo. Investigations into the protein activities of AURKA were conducted using ES cell lines and xenograft models. AURKA was found to be prominently upregulated in ES. The AURKA expression level was remarkably connected to ES patients’ shorter overall survival (OS) and event-free survival (EFS). Furthermore, AURKA inhibition markedly induced the apoptosis and ferroptosis of ES cells and attenuated tumorigenesis in vivo. On the part of potential mechanisms, it was found that AURKA inhibition triggered the apoptosis and ferroptosis of ES cells through the NPM1/Yes1 associated transcriptional regulator (YAP1) axis, which provides new insights into the tumorigenesis of ES. AURKA may be a prospective target for clinical intervention in ES patients.

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“…Therefore, NPM1 can potentially function as a histone chaperone during DNA strand break repair of tumor cells. Furthermore, NSC348884, an NPM1 inhibitor that disrupts oligomer formation and induces apoptosis, has demonstrated antitumor activity in CRC and Ewing sarcoma cells in vitro [ 45 , 128 ]. Further research is required on NPM1 inhibitors in digestive cancers.…”

Section: Histone Chaperones In Digestive Cancersmentioning

confidence: 99%

Histone Chaperones and Digestive Cancer: A Review of the Literature

Zhao

Cai

Jiang

et al. 2022

Cancers

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Background: The global burden of digestive cancer is expected to increase. Therefore, crucial for the prognosis of patients with these tumors is to identify early diagnostic markers or novel therapeutic targets. There is accumulating evidence connecting histone chaperones to the pathogenesis of digestive cancer. Histone chaperones are now broadly defined as a class of proteins that bind histones and regulate nucleosome assembly. Recent studies have demonstrated that multiple histone chaperones are aberrantly expressed and have distinct roles in digestive cancers. Objective: The purpose of this review is to present the current evidence regarding the role of histone chaperones in digestive cancer, particularly their mechanism in the development and progression of esophageal, gastric, liver, pancreatic, and colorectal cancers. In addition, the prognostic significance of particular histone chaperones in patients with digestive cancer is discussed. Methods: According to PRISMA guidelines, we searched the PubMed, Embase, and MEDLINE databases to identify studies on histone chaperones and digestive cancer from inception until June 2022. Results: A total of 104 studies involving 21 histone chaperones were retrieved. Conclusions: This review confirms the roles and mechanisms of selected histone chaperones in digestive cancer and suggests their significance as potential prognostic biomarkers and therapeutic targets. However, due to their non-specificity, more research on histone chaperones should be conducted in the future to elucidate novel strategies of histone chaperones for prognosis and treatment of digestive cancer.

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NPM1 is a Novel Therapeutic Target and Prognostic Biomarker for Ewing Sarcoma

Cited by 4 publications

References 38 publications

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity

AURKA inhibition induces Ewing’s sarcoma apoptosis and ferroptosis through NPM1/YAP1 axis

Histone Chaperones and Digestive Cancer: A Review of the Literature

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