Identification of GRP75 as an Independent Favorable Prognostic Marker of Neuroblastoma by a Proteomics Analysis

Hsu, Wen Ming; Lee, Hsinyu; Juan, Hsueh‐Fen; Shih, Yu-Yin; Wang, Bo Jeng; Pan, Chien‐Yuan; Jeng, Yung Ming; Chang, Hsiu-Hao; Lu, Meng-Yao; Lin, Kai Hsin; Lai, Hong‐Shiee; Chen, Wei Jao; Tsay, Yeou Guang; Liao, Yung Feng; Hsieh, Fon Jou

doi:10.1158/1078-0432.ccr-07-4181

Cited by 30 publications

(20 citation statements)

References 31 publications

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“…For evaluation of the effect of cell differentiation on IMP3 expression, NB cells were treated with 10 lM all-trans retinoic acid (RA). (24) Cells were harvested before and after RA treatment for 1, 3, and 5 days. The protein expression levels of IMP3 were evaluated by Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

Insulin‐like growth factor II mRNA‐binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma

Chen

Jeng

Chang³

et al. 2011

Cancer Science

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Insulin-like growth factor II mRNA-binding protein 3 (IMP3) has been reported to enhance proliferation and invasion in various cancers. The role of IMP3 on neuroblastoma (NB) is unknown. We aimed to clarify the prognostic significance of IMP3 expression in patients with NB. By microarray analysis, high IMP3 expression was found in patients with poor outcome. IMP3 expression in 90 NB samples was analyzed by immunohistochemical staining to correlate with clinical stages, histology, and patient outcome. Positive IMP3 expression was detected in 52 of 90 patients, and was significantly correlated with undifferentiated histology, advanced stages, MYCN amplification, and poor outcome. In subgroups, positive IMP3 expression could predict an even worse prognosis in patients with advanced disease, with normal MYCN status, or with MYCN amplification (P = 0.005, P = 0.001, and P = 0.033, respectively). The IMP3 expression decreased by induction of differentiation with retinoid acid treatment in SK-N-DZ and SK-N-SH cells in vitro. The invasion ability of NB cells also decreased as IMP3 knockdown by using RNA interference in vitro. In summary, high expression of IMP3 in NB might contribute to the undifferentiated phenotype and invasive behaviors, leading to a poor prognosis. Determining IMP3 expression in NB could help to improve a personalized therapy. (Cancer Sci 2011; 102: 2191-2198 N euroblastoma (NB), a common cancer of early childhood that originates from primitive sympathetic neural precursors, has a remarkable heterogeneity of clinical behaviors ranging from spontaneous regression to rapid progression and death. Therapeutic options are proposed according to the Children's Oncology Group risk stratification criteria based on clinical and biological factors, including clinical stage, MYCN status, age at diagnosis, histology, and ploidy status.(1,2) Treatment strategy, which ranges from observation alone to intensive multimodal therapy, depends on the risk stratification of the patient in one of the three subgroups of low-, intermediate-, and high-risk of death. Although several biological and molecular prognostic factors have been identified, amplification of the MYCN oncogene, which occurs in roughly 20% of primary NB, is one of the most powerful prognostic factors in NB.(3) The co-opting neurotrophin pathways including the neurotrophin receptors (TrkA, TrkB, and TrkC) and their ligands (NGF, BDNF, and neurotrophin-3, respectively), which regulate the differentiation, apoptosis, and growth of neural cells, are also important prognosis-related factors in NB.(4) However, some patients with a normal MYCN copy number still present with clinically aggressive progression similar to those with MYCN-amplified tumors, suggesting that other unfavorable molecules determining inferior survival may exist.(5,6)The insulin-like growth factor II mRNA-binding protein 3 (IMP3), also known as L532S or K homology domain-containing protein overexpressed in cancer (KOC), is a member of the RNA-binding protein family that includes IMP1, IMP2...

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Section: Methodsmentioning

confidence: 99%

Insulin‐like growth factor II mRNA‐binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma

Chen

Jeng

Chang³

et al. 2011

Cancer Science

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“…Recently, it has been demonstrated that mortalin translocates into the nucleus, where it interacts with the retinoic acid receptor to augment retinoic acid -elicited neuronal differentiation (Shih et al, 2011). Interestingly, mortalin is upregulated in retinoic acid-treated neuroblastoma cells and in patients suffering from neuroblastoma (Hsu et al, 2008). Experimental studies confirmed that mortalin interacts with the cellular protein p53 Mizukoshi et al, 2001;Wadhwa et al, 2003).…”

Section: The Role Of Mortalin In Cancermentioning

confidence: 97%

Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

Flachbartova¹,

Kováčech²

2013

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Summary. -Heat shock 70kDa protein 9 (HSPA9)/mortalin is a heat-uninducible member of the heat shock 70 protein family. This protein has been attributed many cellular functions, including energy generation, stress response, carcinogenesis and involvement in neurodegenerative diseases, which is well documented by many names it has been given (CSA, MOT, MOT2, GRP75, PBP74, GRP-75, HSPA9B, MGC4500, MTHSP75, and mortalin). As an immortalization marker (hence the name "mortalin") in mouse embryonic fibroblasts cybrids it preferentially segregated with loss of immortality in passaged cells. Mortalin regulates the functions of the tumor suppressor protein p53 and plays important roles in stress response and maintenance of the mitochondria and endoplasmic reticulum. Furthermore, mortalin appears to have roles in membrane trafficking and viral release regulation, since it interacts with Nef protein it is necessary for secretion of exosomal negative factor (Nef) and HIV-1 virus release. Recently, mortalin has been described as a significant player in neurodegenerative diseases. Mutations in HSPA9 gene have been found in Parkinson΄s disease patients; mortalin isoform expression differs in hippocampus of patients with Alzheimer΄s disease and could regulate the β-amyloid toxicity pathway. In this review we summarize the functions of mortalin, its pathological implications in neuronal dysfunction and possible roles in neurodegenerative diseases.Keywords: HSPA9/mortalin/GRP75; mitochondria; cancer; Alzheimer΄s disease * Corresponding author: E-mail: Branislav.Kovacech@savba.sk; phone: +412-2-54788100. Abbreviations: Aβ = beta-amyloid; AD = Alzheimer΄s disease; PD = Parkinson΄s disease; HSPA9 = heat shock 70 kDa protein 9; Hsp = chaperone; MAC = membrane attack complex; Net = negative factor Contents:

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“…19,27 Therefore, expression of B4GALNT3 in all 87 NB tumor tissues was examined by IHC analysis. Positive B4GALNT3 staining was observed specifically in the cytoplasm of ganglion cells of GNB tumor tissues ( Figure 1A); however, expression was negligible in schwannian stromal cells.…”

Section: B4galnt3 Expression Correlates With the Differentiation Statmentioning

confidence: 99%

B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma

Hsu

Che

Liao

et al. 2011

The American Journal of Pathology

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Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for 8% to 10% of all pediatric malignancies. 1 This tumor arises from primitive neuroepithelial cells of the neural crest. 2 The behavior of NB is markedly heterogeneous, ranging from highly undifferentiated tumors with very poor outcomes to welldifferentiated benign ganglioneuroma or NB that may spontaneously regress with favorable prognosis. 3 Half of all patients with newly diagnosed NB are in a high-risk subset with poor overall survival despite intensive therapy. Therefore, it is important to develop useful prognostic tools and to understand NB pathogenesis to help design improved NB therapies.Glycosylation is regulated spatiotemporally during development of the nervous system. 4 Altered carbohydrate structures on tumors are often associated with tumor metastasis and progression. Tumor-associated carbohydrate epitopes commonly found in cancers include GM2,

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Identification of GRP75 as an Independent Favorable Prognostic Marker of Neuroblastoma by a Proteomics Analysis

Cited by 30 publications

References 31 publications

Insulin‐like growth factor II mRNA‐binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma

Insulin‐like growth factor II mRNA‐binding protein 3 expression predicts unfavorable prognosis in patients with neuroblastoma

Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

B4GALNT3 Expression Predicts a Favorable Prognosis and Suppresses Cell Migration and Invasion via β1 Integrin Signaling in Neuroblastoma

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