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GP73 protein level in gastric tumorous samples and adjacent non-tumorous mucosal samples. A) GP73 protein level in gastric tumorous samples and adjacent non-tumorous mucosal samples. B) GP73 mRNA level in the same gastric tumorous samples and adjacent non-tumorous mucosal samples. C) gastric cancer; N: normal).
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Background
Golgi protein 73 (GP73) is a type II Golgi transmembrane protein. It is over-expressed in several cancers, including hepatocellular carcinomas, bile duct carcinomas, lung cancer and prostate cancer. However, there are few reports of GP73 in gastric cancer. This study is aimed at investigating the expression of GP73 and its relationship w...
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Context 1
... expression levels of GP73 relative to GAPDH were much lower in gastric tu- morous tissues (0.259 ± 0.308) than that in non-tumorous mucosal tissues (0.584 ± 0.523; P<0.01; Figure 1). Consist- ent with RT-qPCR, GP73 protein level in gastric tumor samples was significantly lower than that of non-tumorous samples, which was tested by Western blotting (Figure 2). ...Similar publications
Expressions of Survivin and nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB) are associated with a poor prognosis in many malignancies. However, their relationship in hepatocellular carcinoma remains unclear. To investigate the protein expression of Survivin and NF-κB, determine their role in the pathogenesis of hepatocell...
Objective
The aim of this study was to measure the extracellular matrix protein Spondin-2 (SPON2) in hepatocellular carcinoma (HCC) tissues and to determine its potential value as a prognostic indicator by assessing its correlation with clinicopathological variables and survival.
Methods
SPON2 mRNA expression was assessed in 20 matched pairs of HC...
Citations
... Furthermore, the specificity of serum TAT2 expression levels was 95%, suggesting that it may be used as a novel tumor marker. Chen et al (32) reported that GP73 mRNA and protein expression in GC tissues were lower than those of adjacent normal tissues, which was associated with the differentiation degree of GC and the sex of patients. In the present study, serum TAT-2 expression levels decreased in both groups, whereas serum GP73 expression levels increased after treatment. ...
The present study aimed to explore the effectiveness of endoscopic submucosal dissection (ESD) in the treatment of early gastric cancer (EGC) and its effect on serum tumor-associated trypsin-2 (TAT-2) and Golgi protein 73 (GP73) expression levels to provide a reference for the treatment of EGC. TAT-2 is a proteolytic target enzyme for tumor-associated trypsin inhibitor that has been previously reported to enhance invasion by promoting extracellular matrix degradation. GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis. A total of 161 patients with EGC treated at our hospital from April 2013 to February 2014 were selected as the study subjects. Among these, 86 patients underwent ESD (group A) and the remaining 75 underwent endoscopic mucosal resection (group B). Treatment effectiveness, incidence of complications and adverse reactions, operation time, intraoperative blood loss and length of hospital stay, as well as serum TAT-2 and GP73 expression levels, were compared between the two groups. The treatment effectiveness was significantly higher in group A than in group B (P<0.05). However, there was no significant inter-group difference in terms of incidence of complications/adverse reactions (P>0.05). After treatment, serum TAT-2 expression levels decreased in both groups (P<0.05) and serum TAT-2 expression levels were lower in group A than in group B (P<0.05). Furthermore, serum GP73 expression levels were significantly elevated in both groups (P<0.05). Kaplan-Meier survival analysis indicated no significant inter-group difference in the 5-year survival rate (P>0.05). In conclusion, ESD had a good therapeutic effect on EGC and is able to decrease serum TAT-2 expression levels and increase serum GP73 expression levels. The present study was registered into the Chinese Trials Registry (registration no. NCT02157534).
... Most studies showed that GP73 was overexpressed and was correlated with tumor progression and poor survival in patients with several types of cancer including hepatocellular carcinoma, colon cancer [7,8]. The association between GP73 and gastric cancer remains controversial, GP73 was reported to be correlated with tumor differentiation in gastric cancer [9], however, another study found a correlation between GP73 and patients survival [10]. ...
... The relationship between GP73 expression and gastric cancer progression is still controversial. A study from Chen et al. assessed GP73 protein expression by immunohistochemistry in both tumor and non-tumorous gastric mucosal tissue, they found GP73 was down-regulated in gastric cancer, and its expression in gastric cancer was associated with tumor differentiation [9]. Liu et al's study revealed a significant correlation between GP73 expression and clinical stage, lymph node metastasis and venous invasion, thus the study made a conclusion that GP73 expression may be associated with tumor progression [10], However, in the present study, no significant correlation was found between GP73 expression and clinical variables including age, differentiation and TNM stage, this discrepancy may be explained as the following: firstly, a comparatively more gastric cancer samples were enrolled in the present study, the difference of patient clinical characteristics as a selection bias may influence the analysis. ...
Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.
... Studies showed that GP73 upregulation was correlated with tumor progression and a poor survival in several types of cancer, such as hepatocellular carcinoma and colon cancer [7,8]. The role of GP73 in gastric cancer remains unclear, GP73 was reported to be correlated with tumor differentiation in gastric cancer [9]. Others found the correlation between GP73 and patient survival [10]. ...
... The relationship between GP73 expression and gastric cancer progression is inconsistent. For example, a study from Chen et al, by assessing GP73 protein expression in both tumor and nontumorous gastric mucosal tissue, concluded that GP73 was down-regulated in gastric cancer, and its expression in gastric cancer was associated with tumor differentiation [9]. Liu et al. observed a significant correlation between GP73 expression and clinical stage, lymph node metastasis and venous invasion, which suggested that GP73 expression associate with tumor progression [10]. ...
Background：Golgi protein 73 (GP73), a type II Golgi transmembrane protein member, has been detectedover expressed in several cancers. Its expression and potential pathological function remainselusive. This study aims to investigate the GP73 expression level and to explore its prognostic and predictive value for gastric cancer treatment.
Methods：A total of 348 patients with gastric cancer, who undergone surgery between 1999 and 2011,were retrospectively reviewed. GP73 expression in gastric tumor was examined by tissue microarray analysis. The correlations between GP73 expression and neoadjuvant chemotherapy pathological response as well as patient prognosis were analyzed.
Results：GP73expression was not associated with clinicopathologiccharacteristics including tumor size, differentiation and TNM stage. High expression of GP73 was associated with poor pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer.The multivariate analysis showed GP73 expression was an independent predictor for pathological response to neoadjuvant chemotherapy and for prognosis in patient with gastric cancer.
Conclusions：Our results suggest that GP73 is a promising biomarker to identify patients with poor prognosis as well asa promising predictor for the effect of neoadjuvant chemotherapy in gastric cancer.
... Most studies showed that GP73 was overexpressed and was correlated with tumor progression and poor survival in patients with several types of cancer including hepatocellular carcinoma, colon cancer [7,8]. The association between GP73 and gastric cancer remains controversial, GP73 was reported to be correlated with tumor differentiation in gastric cancer [9], however, other study found the correlation between GP73 and patient survival [10]. ...
... The relationship between GP73 expression and gastric cancer progression is still controversial. A study from Chen et al. assessed GP73 protein expression by immunohistochemistry in both tumor and non-tumorous gastric mucosal tissue, they found GP73 was down-regulated in gastric cancer, and its expression in gastric cancer was associated with tumor differentiation [9]. Liu et al's study revealed a significant correlation between GP73 expression and clinical stage, lymph node metastasis and venous invasion, thus the study made a conclusion that GP73 expression may be associated with tumor progression [10], However, in the present study, no significant correlation was found between GP73 expression and clinical variables including age, differentiation and TNM stage, this discrepancy may be explained as the following: firstly, a comparatively more gastric cancer samples was enrolled in the present study, the difference of patient clinical characteristics as a selection bias may influence the analysis. ...
Background：Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is over expressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer.
Methods：A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray (TMA), the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patient prognosis were analyzed.
Results：We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictor for pathological response to neoadjuvant chemotherapy and for prognosis in patient with gastric cancer.
Conclusions：Our results suggest that GP73 is a promising biomarker to identify patients with poor prognosis as well as a promising predictor for the effect of neoadjuvant chemotherapy in gastric cancer.
... 9,77,104-108 GP73 mRNA is expressed at higher levels in bronchial, gastric, colonic and prostate tissues, but with lower or no expression in muscle, white blood cells, lymphoid tissues and hearts. 72,[109][110][111][112][113][114][115][116][117][118] The most densely expressed GP73 site is the digestive tract. It is also expressed in bile duct epithelial cells, tubular monolayer epithelial cells, pulmonary bronchioles, islets and hippocampus. ...
Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis‐Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non‐viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings.
... Golgi protein 73 (GP73, also termed GOLPH2 and GOLM1) is a type II transmembrane protein that resides in the cis-and medial-Golgi cisternae (10,11). It has been reported that elevated expression levels of GP73 occur not only in viral infections (12)(13)(14)(15) but also in certain cancer types, including HCC, lung cancer, gastric cancer and prostate cancer (16)(17)(18)(19)(20)(21). However, most of the pilot studies have focused on the diagnostic value of GP73 in HCC as a potential tumor biomarker (22)(23)(24), and its functional mechanism remains obscure. ...
The transforming growth factor-β1 (TGF-β1) signaling pathways contribute to cell metastasis and epithelial-mesenchymal transition (EMT). Golgi protein 73 (GP73), a type II transmembrane protein in the Golgi apparatus, was initially regarded as a potential biomarker for the diagnosis of Hepatocellular Carcinoma (HCC). Recently, it was reported that GP73 acts as a key oncogene by promoting HCC growth and metastasis. However, the role of GP73 in metastasis, especially when involving signaling pathways, is uncertain. Here, we report that GP73, which is up-regulated in HCC tissues and cell lines, is associated with tumor size, TNM stage, distant metastasis, and vascular invasion. The ectopic overexpression of GP73 increased HCC cell invasion, EMT and metastasis both in vitro and in vivo. Conversely, GP73 knockdown inhibited invasion and EMT. Moreover, GP73 enhanced p-Smad2 and p-Smad3 levels by mediating TGF-β1, thus leading to the promotion of EMT and invasion in HCC cells. In contrast, we used SB431542 (SB) to repress p-Smad2 and p-Smad3 expression, which resulted in a reversion of EMT. Further, when the TGF-β1/Smad pathway was blocked, up-regulation of GP73 still caused an enhanced EMT and invasion, and down-regulation of GP73 resulted in a decreased in EMT and invasion. In clinical HCC samples, GP73 positively correlated with TGF-β1/Smad2, which was up-regulated in HCC. Taken together, our findings highlight the important role of GP73 in regulating EMT and metastasis in HCC partly by targeting TGF-β1/Smad2 signaling, suggesting that GP73 may represent a novel potential therapeutic target and prognostic marker for the treatment and diagnosis of HCC.
... These strategies can promote systemic immune responses against tumors and, together with TRAIL or IL-24, effectively eliminate cancer cells through the induction of apoptosis, thereby playing an important role in killing not only CSCs but also non-CSCs within the same tumor [33] . Moreover, GOLPH2, as a novel tumor biomarker, has been found during the development of certain other tumor types, eg, liver [16] and gastric tumors [34] , implying that GD55 may exert more extensive cytotoxic effects on these tumors. Recent reports have revealed that an interesting plasticity exists between non-CSCs and CSCs in breast carcinomas [35] . ...
GOLPH2 (also called GP73) is a Golgi glycoprotein, which has been identified as a novel tumor marker upregulated in various cancers, including prostate cancer (PCa). GD55 is a novel GOLPH2-regulated oncolytic adenovirus that exhibits a strong killing effect on hepatoma cells. Here, we investigate the antitumor effect of GD55 on prostate cancer stem cell (CSC)-like cells in vitro and in vivo. Prostate CSC-like sphere cells were acquired and enriched by culturing DU145, LNCap or P3 prostate cancer cells in suspension. The prostate CSC-like sphere cells were capable of self-renewal, differentiation and quiescence, displaying tumorigenic feature and chemo-resistance to 5-FU, doxorubicin and DDP. Treatment with GD55 (1, 5, 10 MOI) dose-dependently suppressed the viability of DU145 sphere cells, which was a more pronounced compared to its cytotoxic action on the parental DU145 cells. In a mouse xenograft prostate CSC-like model, intratumoral injection of GD55 markedly suppressed the growth rate of xenograft tumors and induced higher levels of cell death and necrosis within the tumor tissues. Our results demonstrate that GD55 infection exerts strong anticancer effects on prostate CSC-like cells in vitro and in vivo, and has a potential to be used in the clinical therapy of PCa.
... ii) GOLPH3 is an oncogene in many solid tumors (16), and a previous clinical study indicated that GOLPH3 is overexpressed in patients with GC and is associated with poor clinical outcome in GC (17). iii) Apart from GOLPH3, other proteins from the GOLPH family, such as GOLPH2, were identified to be ectopically expressed in GCs (27). iv) Even though a full underlying molecular mechanism was not observed, GOLPH3 was proven to play an essential role in vesicle trafficking and Golgi structure (28). ...
Emerging evidence has shown that microRNAs (miRNAs) play critical roles in tumor development and progression. miR-134 has been found to act as a tumor-suppressor in numerous types of cancers. However, little is known concerning the potential role of miR-134 in gastric carcinogenesis. In the present study, we found that miR-134 was highly downregulated in gastric cancer tissues and cell lines when compared with levels in their adjacent non-tumor tissues and the normal human gastric epithelial cell line GES-1. Additionally, overexpression of miR-134 was accompanied by reduced cell proliferation in vitro and decreased tumor size in vivo. Further investigation by luciferase reporter assay indicated that Golgi phosphoprotein 3 (GOLPH3), a potent oncogene, was a direct target of miR-134. The activity of a luciferase reporter carrying the miR-134 binding site in the 3'-untranslated region (3'-UTR) of GOLPH3 was repressed by overexpression of miR-134, while a mutation in the 3'-UTR of GOLPH3 abrogated this effect, indicating that GOLPH3 is a target gene of miR-134. Overexpression of GOLPH3 blocked the antiproliferative effect of pre-miR-134 in gastric carcinoma cells. Furthermore, overexpression of miR-134 was associated with decreased phosphorylation of AKT, mTOR and S6K. Taken together, these data suggest that miR-134 regulates gastric cancer cell proliferation, at least potentially, through downregulation of the GOLPH3 gene, implicating a candidate tumor-suppressor miRNA in the pathogenesis of gastric cancer.
... Golgi protein 73 (GP73, also termed GOLPH2 and GOLM1) is a 73-kDa type-II Golgi transmembrane glycoprotein that was originally cloned from a library derived from the liver tissue of a patient with adult giant cell hepatitis (7). It is reported that expressions of GP73 increased not only in viral infections (8)(9)(10)(11) but also in certain cancer types, including HCC, prostate cancer, lung cancer, and gastric cancer (12)(13)(14)(15)(16)(17), but more attention has been paid in the aberrant expressions of GP73 in liver diseases. It has been found that GP73 elevated moderately along with the progression of liver disease, from hepatitis to cirrhosis, and then it increased remarkably in HCC (18). ...
Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. Golgi protein 73 (GP73) is a serum biomarker for hepatocellular carcinoma (HCC) and our previous study demonstrated that the expression of GP73 correlated with aggressive behavior and EMT molecules in HCC. However, its role in metastatic mechanism of HCC is not clear. The aim of this study was to investigate the effect of GP73 on invasion and migration, and underlying mechanism of GP73 involved in EMT of HCC. The expression of GP73 was downregulated by small interfering RNA (siRNA). The metastatic and invasive abilities were analyzed using scratch assay and Transwell assay. Changes in EMT-related molecules were evaluated by western blot and qRT‑PCR analyses, and epithelial-mesenchymal phenotype changes were also observed. Expression of GP73 was upregulated in the more metastatic HCC cell lines. Knockdown of GP73 by siRNA resulted in a significant decrease in migratory and invasive abilities in both MHCC97H and Bel-7404 cell lines. Importantly, EMT-related markers and morphological phenotypes significantly changed following by the inhibition of GP73. Silencing GP73 contributed to the reduction of invasion and metastasis via suppressing EMT in HCC. GP73 may serve as a novel molecular target against EMT in HCC metastasis therapy.
... The introduction of immune promoting genes such as GM-CSF can promote the immune responses against tumors, and delivery of TRAIL or IL-24 gene effectively eliminates cancer cells through apoptosis, playing aim portant killing roles not only in CSCs, but also non-CSCs [8,36]. Moreover, GP73, as a novel tissue biomarker, also is founded to occur in the development process of prostate cancer [37] and is down-regulated in gastric cancer and associated with tumor differentiation [38]; implying that GD55 has different effect for other types of cancers. ...
Cancer stem cells (CSCs), also known as tumor-initiating cells, are highly metastatic, chemo-resistant and tumorigenic, and are critical for cancer development, maintenance and recurrence. Oncolytic adenovirus could targetedly kill CSCs and has been acted as a promising anticancer agent. Currently, a novel GP73-regulated oncolytic adenovirus GD55 was constructed to specifically treat liver cancer and exhibited obvious cytotoxicity effect. However, there remains to be confirmed that whether GD55 could effectively eliminate liver CSCs. We first utilized the suspension culture to enrich the liver CSCs-like cells, which acquires the properties of liver CSCs in self-renewal, differentiation, quiescence, chemo-resistance and tumorigenicity. The results indicated that GD55 elicited more significant cytotoxicity and stronger oncolytic effect in liver CSC-like cells compared to common oncolytic virus ZD55. Additionally, GD55 possessed the greater efficacy in suppressing the growth of implanted tumors derived from liver CSC-like cells than ZD55. Furthermore, GD55 induced remarkable apoptosis of liver CSC-like cells in vitro and in vivo, and inhibited the propogation of cells and angiogenesis in xenograft tumor tissues. Thus, GD55 may virtually represent an attractive therapeutic agent for targeting liver CSCs to achieve better clinical outcomes for HCC patients.
