What's Nu(SAP) in mitosis and cancer?

Iyer, Jyoti; Moghe, Saili; Furukawa, Megumi; Tsai, Ming Ying

doi:10.1016/j.cellsig.2010.11.006

Cited by 48 publications

(47 citation statements)

References 42 publications

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“…Surprisingly, little work has examined the role of NUSAP1 in cancer, despite several reports documenting that overexpression of NUSAP1 is associated with significantly worse outcome [55]. Given its critical role in mitosis, knockdown of NUSAP1 results in decreased proliferation, cell cycle arrest in G2/M, and induction of apoptosis [26, 56, 57], as we have observed here.…”

Section: Discussionsupporting

confidence: 63%

“…NUSAP1 is a highly validated biomarker of prostate cancer progression [11, 13–16] and overexpressed in multiple cancer types [55]. Our analyses of prostate cancer cell lines and prostate cancer patient samples suggest that NUSAP1 is more than just a prognostic biomarker in prostate cancer, but actually plays a role in driving prostate cancer progression.…”

Section: Discussionmentioning

confidence: 88%

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NUSAP1 promotes invasion and metastasis of prostate cancer

et al. 2017

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We have previously identified nucleolar and spindle associated protein 1 (NUSAP1) as a prognostic biomarker in early stage prostate cancer. To better understand the role of NUSAP1 in prostate cancer progression, we tested the effects of increased and decreased NUSAP1 expression in cell lines, in vivo models, and patient samples. NUSAP1 promotes invasion, migration, and metastasis, possibly by modulating family with sequence similarity 101 member B (FAM101B), a transforming growth factor beta 1 (TGFβ1) signaling effector involved in the epithelial to mesenchymal transition. Our findings provide insights into the importance of NUSAP1 in prostate cancer progression and provide a rationale for further study of NUSAP1 function, regulation, and clinical utility.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 88%

NUSAP1 promotes invasion and metastasis of prostate cancer

et al. 2017

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“…Therefore, like AR, NuSAP could represent another important effector protein in the Rb-E2F regulatory pathway in prostate cancer. In addition, the activation and release of NuSAP from Imp α, Imp β, and Imp 7 is mediated by RANGTP, an AR regulated gene (46). Therefore, NuSAP over-expression could cooperate to AR signaling in prostate cancer progression (Figure 7).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of NuSAP in recurrent prostate cancer is mediated by E2F1

2012

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Increasing evidence suggests that prostate cancer is over diagnosed and over treated, and prognostic biomarkers would aid in treatment selection. To define prognostic biomarkers for aggressive prostate cancer, we carried out gene expression profiling of 98 prostate tumors and 52 benign adjacent prostate tissue samples with detailed clinical annotation. We identified 28 transcripts significantly associated with recurrence after radical prostatectomy including NuSAP, a protein that binds DNA to the mitotic spindle. Elevated NuSAP transcript levels were associated with poor outcome in 2 independent prostate cancer gene expression datasets. To characterize the role and regulation of NuSAP in prostate cancer, we studied the expression of NuSAP in the LNCaP and PC3 human prostate cancer cell lines. Post-transcriptional silencing of the NuSAP gene severely hampered the ability of PC3 to invade and proliferate in vitro. The promoter region of the NuSAP gene contains 2 CCAAT boxes and binding sites for E2F. Transient transfection of an E2F1 cDNA and 431 bp of the NuSAP promoter demonstrated E2F1 as an important regulator of expression. Deletion of the E2F binding site at nt −246 negated the effects of E2F1 on NuSAP expression. Electrophoretic mobility shift assays demonstrated that nuclear extracts of cells over-expressing E2F1 bound directly to the E2F binding site in the NuSAP promoter region. Finally, immunohistochemistry showed a strong correlation between E2F1 and NuSAP expression in human prostate cancer samples. NuSAP is a novel biomarker for prostate cancer recurrence after surgery and its over-expression appears to be driven in part by E2F1 activation.

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“…NuSAP is a microtubule-associated protein that bundles and stabilizes microtubules thereby linking chromosomes to the mitotic spindle [35]. Recently, overexpression of NUSAP1 has been found in various human cancers by array analysis, including glioblastomas, hepatocellular carcinomas, pancreatic adenocarcinoma (reviewed in [21]). The high expression of the NUSAP1 gene has been associated with poor prognosis in melanoma patients [3], with a malignancy-risk genetic signature in breast cancer [4] and with recurrence in prostate cancer [15].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of MENX-associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas

et al. 2013

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Gonadotroph adenomas comprise 15–40 % of all pituitary tumors, are usually non-functioning and are often large and invasive at presentation. Surgery is the first-choice treatment, but complete resection is not always achieved, leading to high recurrence rates. As gonadotroph adenomas poorly respond to conventional pharmacological therapies, novel treatment strategies are needed. Their identification has been hampered by our incomplete understanding of the molecular pathogenesis of these tumors. Recently, we demonstrated that MENX-affected rats develop gonadotroph adenomas closely resembling their human counterparts. To discover new genes/pathways involved in gonadotroph cells tumorigenesis, we performed transcriptome profiling of rat tumors versus normal pituitary. Adenomas showed overrepresentation of genes involved in cell cycle, development, cell differentiation/proliferation, and lipid metabolism. Bioinformatic analysis identified downstream targets of the transcription factor SF-1 as being up-regulated in rat (and human) adenomas. Meta-analyses demonstrated remarkable similarities between gonadotroph adenomas in rats and humans, and highlighted common dysregulated genes, several of which were not previously implicated in pituitary tumorigenesis. Two such genes, CYP11A1 and NUSAP1, were analyzed in 39 human gonadotroph adenomas by qRT-PCR and found to be up-regulated in 77 and 95 % of cases, respectively. Immunohistochemistry detected high P450scc (encoded by CYP11A1) and NuSAP expression in 18 human gonadotroph tumors. In vitro studies demonstrated for the first time that Cyp11a1 is a target of SF-1 in gonadotroph cells and promotes proliferation/survival of rat pituitary adenoma primary cells and cell lines. Our studies reveal clues about the molecular mechanisms driving rat and human gonadotroph adenomas development, and may help identify previously unexplored biomarkers for clinical use.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-013-1132-7) contains supplementary material, which is available to authorized users.

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What's Nu(SAP) in mitosis and cancer?

Cited by 48 publications

References 42 publications

NUSAP1 promotes invasion and metastasis of prostate cancer

NUSAP1 promotes invasion and metastasis of prostate cancer

Increased expression of NuSAP in recurrent prostate cancer is mediated by E2F1

Transcriptome analysis of MENX-associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas

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