NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR

Zhao, Yuzu; Jiang, He; Li, Yongsen; Lv, Sheng‐Qing; Cui, Hongjuan

doi:10.1038/s41392-020-0137-7

Cited by 54 publications

(42 citation statements)

References 46 publications

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“…Cells were collected and then lysed in a RIPA lysis buffer with phenylmethanesulfonyl fluoride (PMSF) as previously described [ 31 ]. Protein concentration was detected with a BCA protein assay kit.…”

Section: Methodsmentioning

confidence: 99%

Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

Deng

Pan

et al. 2020

J Exp Clin Cancer Res

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Background Lycorine hydrochloride (LH), an alkaloid extracted from the bulb of the Lycoris radiata, is considered to have anti-viral, anti-malarial, and anti-tumorous effects. At present, the underlying mechanisms of LH in gastric cancer remain unclear. MCL1, an anti-apoptotic protein of BCL2 family, is closely related to drug resistance of tumor. Therefore, MCL1 is considered as a potential target for cancer treatment. Methods The effect of LH on gastric cancer was assessed in vitro (by MTT, BrdU, western blotting…) and in vivo (by immunohistochemistry). Results In this study, we showed that LH has an anti-tumorous effect by down-regulating MCL1 in gastric cancer. Besides, we unveiled that LH reduced the protein stability of MCL1 by up-regulating ubiquitin E3 ligase FBXW7, arrested cell cycle at S phase and triggered apoptosis of gastric cancer cells. Meanwhile, we also demonstrated that LH could induce apoptosis of the BCL2-drug-resistant-cell-lines. Moreover, PDX (Patient-Derived tumor xenograft) model experiment proved that LH combined with HA14–1 (inhibitor of BCL2), had a more significant therapeutic effect on gastric cancer. Conclusions The efficacy showed in our data suggests that lycorine hydrochloride is a promising anti-tumor compound for gastric cancer.

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Section: Methodsmentioning

confidence: 99%

Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

Deng

Pan

et al. 2020

J Exp Clin Cancer Res

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“…The shNUCKS sequences (Table S1 ) were inserted into the pLKO.1 vector. As described previously, the cDNA sequence of human NUCKS was purchased from Youbio Biological Technology Co., Ltd. (Changsha, China), which was cloned into the pCDH-CMV-MCS-EF1-GFP-Puro vector provided by GeneCreate (Wuhan, China) [ 27 ]. The Beclin1 shRNA plasmid was purchased from Sigma-Aldrich (TRCN0000299864), and the plasmid GFP-LC3B [ 28 ] was a gift from Prof. Ning Gao at the Third Military Medical University, China.…”

Section: Methodsmentioning

confidence: 99%

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

Zhao

Feng

Bai

et al. 2020

J Exp Clin Cancer Res

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Background Nuclear casein kinase and cyclin-dependent kinase substrate (NUCKS), a novel gene first reported in 2001, is a member of the high mobility group (HMG) family. Although very little is known regarding the biological roles of NUCKS, emerging clinical evidence suggests that the NUCKS protein can be used as a biomarker and therapeutic target in various human ailments, including several types of cancer. Methods We first assessed the potential correlation between NUCKS expression and gastric cancer prognosis. Then functional experiments were conducted to evaluate the effects of NUCKS in cell proliferation, cell cycle, apoptosis and autophagy. Finally, the roles of NUCKS on gastric cancer were examined in vivo. Results We found that NUCKS was overexpressed in gastric cancer patients with poor prognosis. Through manipulating NUCKS expression, it was observed to be positively associated with cell proliferation in vitro and in vivo. NUCKS knockdown could induce cell cycle arrest and apoptosis. Then further investigation indicated that NUCKS knockdown could also significantly induce a marked increase in autophagy though the mTOR-Beclin1 pathway, which could be was rescued by NUCKS restoration. Moreover, silencing Beclin1 in NUCKS knockdown cells or adding rapamycin in NUCKS-overexpressed cells also confirmed these results. Conclusions Our findings revealed that NUCKS functions as an oncogene and an inhibitor of autophagy in gastric cancer. Thus, the downregulation or inhibition of NUCKS may be a potential therapeutic strategy for gastric cancer.

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“…17 Accumulating evidence have indicated that abnormal expression of NUSAP1 was implicated in tumorigenesis, drug resistance and patient survival. [18][19][20] Li et al reported that NUSAP1 contributed to cervical cancer via stimulating cancer stem cell (CSC) traits and facilitating epithelialmesenchyme transition (EMT) progression via Wnt/βcatenin signaling. 21 Furthermore, Okamoto et al found that NUSAP1 expression was upregulated in Oral Squamous Cell Carcinoma (OSCC)-derived cell lines and knockdown of NUSAP1 inhibited cell proliferation and also promoted anti-tumor effect of Paclitaxel by inducing apoptosis in OSCC.…”

Section: Dovepressmentioning

confidence: 99%

NUSAP1 Accelerates Osteosarcoma Cell Proliferation and Cell Cycle Progression via Upregulating CDC20 and Cyclin A2

Wang¹,

Liu²,

Wu³

et al. 2021

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Purpose: Nucleolar and spindle-associated protein 1 (NUSAP1) is a significant mitotic regulator and has been found to be implicated in carcinogenesis of several cancers. The aim of this study was to explore the functional role and underlying mechanisms of NUSAP1 in osteosarcoma. Methods: Western blot assay and Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) were employed to assess the expressions of NUSAP1, cell division cycle 20 homologue (CDC20) and cyclin A2 (CCNA2) in osteosarcoma cells. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and 5-ethynyl-2′-deoxyuridine (EdU) assay, and flow cytometry was applied for exploring cell cycle. In addition, an osteosarcoma tumor-bearing mouse model was established by injection of transfected osteosarcoma cells. Tumor volume and protein expressions of Ki67 and PCNA were examined. Bioinformatics analysis and immunoprecipitation were used to identify the combination of NUSAP1 with CDC20 and CCNA2. Results: The mRNA and protein expression of NUSAP1 were extremely upregulated in osteosarcoma cells. Overexpression of NUSAP1 promoted whereas NUSAP1 silencing suppressed cell proliferation and cell cycle progression in transfected osteosarcoma cells. In osteosarcoma mouse model, NUSAP1 expression affected tumor volume and levels of Ki67 and PCNA. Moreover, CDC20 or CCNA2 silencing inhibited NUSAP1-induced cell proliferation and cell cycle in osteosarcoma cells. Conclusion:Our data demonstrated that upregulated NUSAP1 may exacerbate the development of osteosarcoma by accelerating the proliferation and cell cycle process of osteosarcoma cells by binding to CDC20 and CCNA2, suggesting NUSAP1 as a possible therapeutic target for treatment of osteosarcoma.

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NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR

Cited by 54 publications

References 46 publications

Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

Lycorine hydrochloride inhibits cell proliferation and induces apoptosis through promoting FBXW7-MCL1 axis in gastric cancer

NUCKS promotes cell proliferation and suppresses autophagy through the mTOR-Beclin1 pathway in gastric cancer

NUSAP1 Accelerates Osteosarcoma Cell Proliferation and Cell Cycle Progression via Upregulating CDC20 and Cyclin A2

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