The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor

Otani, Satoshi; Takeda, Shin; Yamada, Suguru; Sakakima, Yoshikazu; Sugimoto, Hiroyuki; Nomoto, Shuji; Kasuya, Hideki; Kanazumi, Naohito; Nagasaka, Tetsuo; Nakao, Akimasa

doi:10.1002/jso.21241

Cited by 23 publications

(25 citation statements)

References 15 publications

(13 reference statements)

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“…We observed a decrease in NPRL2 mRNA level in 45.45% of the colon cancer patients. Downregulation of NPRL2 has been reported for some cancers such as non-smallcell lung carcinoma (NSCLC), hepatocellular carcinoma (HCC), and esophageal squamous cell carcinoma at different frequencies (Yi-Lo et al, 2006;Otani et al, 2009;Senchenko et al, 2010). The downregulation rate in our study is similar to the levels observed in HCC and esophageal squamous cell carcinoma (ESCC), but it is lower than the rates described for NSCLC (Yi-Lo et al, 2006;Otani et al, 2009;Senchenko et al, 2010).…”

Section: Discussionsupporting

confidence: 69%

“…Most of the tumors in our study group (69%) were adenocarcinomas, and NPRL2 expression was similarly downregulated in 45.5% of this subgroup. Otani et al (2009) reported similar NPRL2 expression levels in both normal liver and HCC tumor tissues. However, when they analyzed NPRL2 expression according to the clinicopathological characteristics of the patients, they revealed that low NPRL2 expression levels are correlated with shorter overall and disease-free survival in HCC patients (Otani et al, 2009).…”

Section: Discussionmentioning

confidence: 76%

“…Otani et al (2009) reported similar NPRL2 expression levels in both normal liver and HCC tumor tissues. However, when they analyzed NPRL2 expression according to the clinicopathological characteristics of the patients, they revealed that low NPRL2 expression levels are correlated with shorter overall and disease-free survival in HCC patients (Otani et al, 2009). In our study group, the expression levels in normal and tumor tissues were different but the difference was not statistically significant.…”

Section: Discussionmentioning

confidence: 76%

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NPRL2 gene expression in the progression of colon tumors

Yogurtcu

Hatemı²,

Aydın³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Genetic and epigenetic factors affecting DNA methylation and gene expression are known to be involved in the development of colon cancer, but the full range of genetic alterations and many key genes involved in the pathogenesis of colon cancer remain to be identified. NPRL2 is a candidate tumor suppressor gene identified in the human chromosome 3p21.3 region. We evaluated the role of this gene in the pathogenesis of colorectal cancer by investigating NPRL2 mRNA expression in 55 matched normal and tumor colon tissue samples using quantitative RT-PCR analysis. There was significantly decreased NPRL2 expression in 45% of the patients. Lower NPRL2 expression was observed significantly more frequently in poorly differentiated tumor samples than in highly or moderately differentiated tumors. We conclude that expression of NPRL2 contributes to progression of colon cancer.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 76%

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NPRL2 gene expression in the progression of colon tumors

Yogurtcu

Hatemı²,

Aydın³

et al. 2012

Genet. Mol. Res.

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“…Various mutations of Nprl2 have been detected in different tumors, including lung cancer (66) and hepatocellular carcinoma (67). Nprl2 and Depdc5 (the human homolog of Sea1) are also deregulated in ovarian cancers and glioblastomas (21,68).…”

Section: Discussionmentioning

confidence: 99%

Molecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway

Algret

Fernández-Martı́nez

Shi

et al. 2014

Molecular & Cellular Proteomics

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The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway. Molecular & Cellular

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“…More than a decade ago, Nprl2 was suggested to be a tumor suppressor (Lerman and Minna, 2000). Since then, low levels of Nprl2 expression have been detected in many cancers, including hepatocellular carcinoma (Otani et al, 2009), glioblasomas (Bar-Peled et al, 2013, as well as in lung (Anedchenko et al, 2008;Ji et al, 2002;Li et al, 2004;Ueda et al, 2006), ovarian Li et al, 2004), renal (Li et al, 2004;Tang et al, 2014), colorectal (Liu et al, 2014;Yogurtcu et al, 2012) and breast cancers (Li et al, 2004). In addition, it has been reported that Nprl2 interacts with the kinase Pdk1, a key regulator of cell proliferation and survival (Kurata et al, 2008).…”

Section: Deregulation Of Gator In Cancer and Other Diseasesmentioning

confidence: 99%

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

Dokudovskaya

Rout

2015

Journal of Cell Science

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Cells constantly adapt to various environmental changes and stresses. The way in which nutrient and stress levels in a cell feed back to control metabolism and growth are, unsurprisingly, extremely complex, as responding with great sensitivity and speed to the 'feast or famine, slack or stress' status of its environment is a central goal for any organism. The highly conserved target of rapamycin complex 1 (TORC1) controls eukaryotic cell growth and response to a variety of signals, including nutrients, hormones and stresses, and plays the key role in the regulation of autophagy. A lot of attention has been paid recently to the factors in this pathway functioning upstream of TORC1. In this Commentary, we focus on a major, newly discovered upstream regulator of TORC1 -the multiprotein SEA complex, also known as GATOR. We describe the structural and functional features of the yeast complex and its mammalian homolog, and their involvement in the regulation of the TORC1 pathway and TORC1-independent processes. We will also provide an overview of the consequences of GATOR deregulation in cancer and other diseases.

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The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factor

Abstract: Our results suggest that NPRL2 mRNA expression has prognostic significance for the survival of patients with HCC.

Cited by 23 publications

References 15 publications

NPRL2 gene expression in the progression of colon tumors

NPRL2 gene expression in the progression of colon tumors

Molecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

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