机构：[1]State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.临床科室其他部门临床研究部/药物临床试验机构华南肿瘤学国家重点实验室中山大学肿瘤防治中心[2]Department of Anatomy, Medical School of Yangtzeu University, Guangzhou, China.[3]Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.外科科室神经外科中山大学附属第一医院[4]Neurosurgical Research Institute, the First Affiliated Hospital of Guangdong Pharmaceutics University, Guangzhou 510060, China.[5]Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.[6]Guangdong Province Key Laboratory of Brain Function and Disease, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Background: The prognosis of human astrocytoma is poor, and the molecular alterations underlying its pathogenesis still needed to be elucidated. Nucleolar and spindle associated protein 1 (NUSAP1) was observed in several types of cancers, but its role in astrocytoma remained unknown. Methods: The expression of NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were analyzed by immunochemistry to demonstrate the correlation between the NUSAP1 expression and clinicopathological characteristics. 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay, colony formation, transwell matrix penetration assay, wound healing assay and anchorage-independent growth assay were used to investigate the biological effect of NUSAP1 in astrocytoma. An intracranial brain xenograft tumor model was used to confirm the oncogenic role of NUSAP1 in human astrocytoma. Luciferase reporter assay was used to investigate the effect of NUSAP1 on Hedgehog signaling pathway. Results: NUSAP1 was markedly overexpressed in astrocytoma cell lines and tissues compared with normal astrocytes and brain tissues. NUSAP1 was found to be overexpressed in 152 of 221 (68.78%) astrocytoma tissues, and was significantly correlated to poor survival. Further, ectopic expression or knockdown of NUSAP1 significantly promoted or inhibited, respectively, the invasive ability of astrocytoma cells. Moreover, intracranial xenografts of astrocytoma cells engineered to express NUSAP1 were highly invasive compared with the parental cells. With regard to its molecular mechanism, upregulation of NUSAP1 in astrocytoma cells promoted the nuclear translocation of GLI family zinc finger 1 (GLI1) and upregulated the downstream genes of the Hedgehog pathway. Conclusion: These findings indicate that NUSAP1 contributes to the progression of astrocytoma by enhancing tumor cell invasiveness via activation of the Hedgehog signaling pathway, and that NUSAP1 might be a potential prognostic biomarker as well as a target in astrocytoma.
基金：
This work was supported by the Ministry of Science and Technology of
China grant (973 Program, No. 2014CB91060); and the Natural Science
Foundation of China (No. 81773106, 81,325,013, 81,530,082, 91,529,301,
81,672,874 and 81,621,004); the Science and Technology of Guangdong
Province (No.2016A030308002, 2015A030313468, 2014A030313008 and
2014A030313220); the Distinguished Young Scholar of Guangdong Province,
China (No. 2015A030306033); the Innovative Academic Team of Guangzhou
Education System (No. 1201610014); Guangdong science and technology
innovation young top-notch talent (No. 2016TQ03R801); the Guangzhou
scholars research projects of Guangzhou municipal colleges and universities
(No. 12A009D).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|2 区肿瘤学
最新[2023]版：
大类|1 区医学
小类|2 区肿瘤学
第一作者：
第一作者机构：[1]State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
共同第一作者：
通讯作者：
通讯机构：[1]State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.[4]Neurosurgical Research Institute, the First Affiliated Hospital of Guangdong Pharmaceutics University, Guangzhou 510060, China.
推荐引用方式(GB/T 7714)：
Xianqiu Wu,Benke Xu,Chao Yang,et al.Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2017,36(1):-.doi:10.1186/s13046-017-0597-y.
APA：
Xianqiu Wu,Benke Xu,Chao Yang,Wentao Wang,Dequan Zhong...&Wei Zhang.(2017).Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,36,(1)
MLA：
Xianqiu Wu,et al."Nucleolar and spindle associated protein 1 promotes the aggressiveness of astrocytoma by activating the Hedgehog signaling pathway".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 36..1(2017):-
医学