Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis

Qu, Danni; Qu, Huamin; Fu, Ming; Zhao, Xuelian; Liu, Rong; Li-hua, Sui; Zhan, Qimin

doi:10.1016/j.ygyno.2008.04.015

Cited by 21 publications

(31 citation statements)

References 31 publications

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“…Following introduction of exogenous Nlp into ovarian cancer SKOV3 cells, the cell death induced by the chemotherapeutic agent Taxol, which is thought to induce apoptosis by stabilizing the spindle microtubules and causing mitotic arrests at the metaphase stage, is substantially inhibited (41). In support of these findings, we have shown that MEFs derived from Nlp transgenic mice exhibit resistance to apoptosis activated by IR and UV radiation ( Figure 7D).…”

Section: Discussionsupporting

confidence: 66%

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

Shao¹,

Liu²,

Wang³

et al. 2010

J. Clin. Invest.

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Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

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Section: Discussionsupporting

confidence: 66%

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

Shao¹,

Liu²,

Wang³

et al. 2010

J. Clin. Invest.

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“…Previously, Qu et al examined the expression of Nlp in human ovarian cancer and found that overexpression of Nlp counteracted the apoptosis of ovarian cancer cells induced by paclitaxel (12). Similar findings have also been reported for other centrosome-associated proteins.…”

Section: Discussionsupporting

confidence: 66%

“…Recent studies have described overexpression of Nlp in several types of human tumors and suggested it was a potential oncogenic protein (11,12). In this study, we have shown for the first time that Nlp, a novel centrosome-associated protein, is overexpressed in human HNSCC.…”

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

“…Overexpression of Nlp caused aberrant spindle formation, suggesting that Nlp is a key regulator in centrosome maturation, which contributes to chromosome segregation and cytokinesis (8-11). Recent observations indicate that Nlp is deregulated in several types of human solid tumors (11,12), suggesting a role of this novel centrosome protein in the process of tumorigenesis.In the current study, we analyzed the expression of Nlp in 76 primary HNSCC and associated non-neoplastic squamous epithelium. The correlations of Nlp overexpression with ONCOLOGY REPORTS 22: 789-798, 2009 …”

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confidence: 99%

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Ninein-like protein is overexpressed in head and neck squamous cell carcinoma and contributes to cancer growth and resistance to apoptosis

Zhan¹

2009

Oncol Rep

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Abstract. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and survival rates are not improving. Better understanding of the molecular mechanisms of this disease becomes critical to develop more effective treatments. Ninein-like protein (Nlp), a recently identified centrosome-associated protein, is a key regulator in centrosome maturation, which contributes to chromosome segregation and cytokinesis. Recent studies have revealed overexpression of Nlp in several types of human tumors and suggested it was a potential oncogenic protein. To investigate the role of Nlp in the development of HNSCC, expression of Nlp in tumor tissues of 76 HNSCC patients were analyzed, and the correlations of Nlp expression with the clinicopathological characteristics were evaluated. Our data showed overexpression of Nlp in tumor tissues compared with their normal counterparts. Moreover, overexpression of Nlp correlated with tumor differentiation and immunohistochemistry analysis of preinvasive dysplasia and squamous cell carcinoma showed that overexpression of Nlp occurred in premalignant lesions. Biological studies with human HNSCC cell lines indicated that overexpression of Nlp promoted cell proliferation and inhibited cisplatin-induced apoptosis. Taken together, these results suggest a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of HNSCC and support the notion that Nlp overexpression might contribute to the development of HNSCC. IntroductionHead and neck squamous cell carcinoma (HNSCC) accounts for most cancers of the mouth, pharynx and larynx (1). It represents the sixth most frequent cancer worldwide, with an estimated 900,000 cases diagnosed each year (2). Despite advances in surgical and other treatments, HNSCC is still a devastating disease as the survival rates virtually have not changed for the past 30 years (3). While the relatively favorable prognosis for patients diagnosed with early stage HNSCC, >60% of patients apply to hospitals are of advanced stages and the 5-year survival rate for HNSCC patients in stages III and IV (Union International Contre Cancer stages) is <40% (4). Currently, much effort is focused on developing novel strategies for early detection, classification, prevention and treatment of the disease. To fulfill this purpose, a better understanding of the molecular mechanism of HNSCC is underscored.Previously, centrosome amplification have been implicated in the pathogenesis of many types of solid tumors, including HNSCC (5-7). Because centrosomes direct the formation of spindles for the correct separation of chromosomes during mitosis, the presence of more than two centrosomes in a cell can result in lost or fragmented chromosomes after cell division and generation of aneuploidy, which are closely associated with cell transformation and tumorigenesis (7). Ninein-like protein (Nlp), a recently identified centrosomal protein, locates at chromosome 20. During interphase, Nlp is involved in microtubule organization. Two ...

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Copy number and expression of CEP89, a protein required for ciliogenesis, are increased and predict poor prognosis in patients with ovarian cancer

Berkel

Çaçan

2022

Cell Biochemistry & Function

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CEP89 (centrosomal protein 89) is required for ciliogenesis and mitochondrial metabolism, but its role in cancer has yet to be clarified. We report that CEP89 is overexpressed in ovarian cancer (OC) compared to normal ovaries. Likewise, its expression is higher in malignant ovarian tumors than in borderline ovarian tumors with low malignant potential. More than a quarter of patients with OC have copy number gains in the CEP89 gene, and patients with high expression have more than a year shorter overall survival compared to those with low expression. Moreover, we found that CEP89 can be considered as a prognostic marker for poor overall survival in patients with OC, after adjusting for tumor stage and residual tumor. Nine out of the top 10 protein interactors of CEP89 have the highest percentage of total copy number variation (CNV) events in OC among all other cancer types. Furthermore, CEP89 messenger RNA (mRNA) levels are higher in OC patients with disease recurrence compared to those with no recurrence. We also analyzed CEP89 levels in OC cell lines in terms of CNV, mRNA, and protein levels; and observed that the FUOV-1 cell line has the highest levels among cell lines that originated from primary sites. Our study suggests that CEP89 may be a valuable prognostic predictor for the overall survival of patients with OC, and it could also be a novel therapeutic target in this malignancy.

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Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis

Cited by 21 publications

References 31 publications

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

Ninein-like protein is overexpressed in head and neck squamous cell carcinoma and contributes to cancer growth and resistance to apoptosis

Copy number and expression of CEP89, a protein required for ciliogenesis, are increased and predict poor prognosis in patients with ovarian cancer

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