Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance

Chen, Chi-De; Wang, Chia‐Siu; Huang, Ya‐Hui; Chien, Kun-Yi; Li, Ying; Chen, Wen‐Jone; Lin, Kwang‐Huei

doi:10.1002/pmic.200600663

Cited by 104 publications

(99 citation statements)

References 37 publications

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“…In accordance with our study elevated CLIC1 levels have been reported in hepatocellular carcinoma (Huang et al, 2004) and gastric carcinoma (Chen et al, 2007) and in gastric cancer this was strongly correlated with lymph node metastasis, lymphatic invasion, perineural invasion and pathological staging indicating that CLIC1 could be a potential prognostic marker (Chen et al, 2007). Otherwise, the literature contains little data on this protein and its relationship to cancer.…”

Section: Other Proteinssupporting

confidence: 61%

Differential tissue-specific protein markers of vaginal carcinoma

et al. 2009

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The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin -proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.

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Section: Other Proteinssupporting

confidence: 61%

Differential tissue-specific protein markers of vaginal carcinoma

et al. 2009

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“…Details of the 2-DE and mass spectrometric analysis have been described previously. (8) Western blot analysis. Western blot analysis was performed as described previously.…”

Section: Methodsmentioning

confidence: 99%

Glucose‐regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer

Liao

Huang

et al. 2011

Cancer Science

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Human papilloma virus infection is critical but not sufficient to cause cervical cancer. Molecular markers of cervical carcinogenesis are essential. The aim of this study was to identify aberrantly expressed proteins in cervical cancer and determine their clinical significance. A two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomic strategy was used for screening candidate proteins. Immunoblotting and immunohistochemical (IHC) analyses were performed to confirm the results of 2-DE, and the clinical significance was estimated. Glucose-regulated protein 58 (Grp58) was overexpressed in 73% of cancers. The IHC staining showed that the Grp58 histoscore was significantly higher in patients with adenocarcinoma (AD) compared with squamous cell carcinoma (P < 0.05). Grp58 staining was intense in AD with a penetration depth greater than half of the cervical stroma (P = 0.033). High Grp58 expression was associated with low overall survival and recurrence-free survival (RFS) rates (P = 0.007 and P = 0.013, respectively). In multivariate analysis, high Grp58 expression (P = 0.042) and lymph node metastasis (P = 0.026) were determined as independent prognostic factors for RFS. Patients exhibiting both high Grp58 expression and lymph node metastasis displayed poorer outcomes than the other patient groups. In functional studies, knockdown of Grp58 in HeLa cells led to decreased cell invasiveness and inhibition of lung metastasis in a xenograft mouse model. In conclusion, Grp58 serves as a potent prognostic factor of cervical AD. Estimation of the Grp58 index in conjunction with the lymph node metastasis status might aid in predicting the prognosis of cervical AD. (Cancer Sci 2011; 102: 2255-2263 C ervical cancer is one of the most common cancers among women worldwide. Approximately 500 000 diagnoses of cervical cancer are made each year, leading to 274 000 deaths, although the incidence and death rate have declined markedly in the past three decades because of effective screening.(1) Human papillomaviruses (HPV) are the causative agents of over 99% of cervical cancers containing viral sequences. Infection by highrisk HPV types is necessary but not sufficient for progression to cancer. Most HPV infections are transient without clinical manifestation and are cleared naturally; <1% of women become HPV carriers and remain at high risk of developing cervical cancer.(2)The mechanisms underlying the progression and regression of lesions caused by HPV infection are unknown, and further investigation of the molecular alterations in cervical cancer is needed.Glucose-regulated protein 58 (Grp58) is a glycoprotein-specific thiol-oxidoreductase belonging to the disulfide isomerase family of proteins. Grp58 is a multifunctional protein.(3) Recent studies suggest that Grp58 plays a role in cancer, although related information is limited. Hirano et al.(4) demonstrated that enhanced expression of Grp58 was associated with oncogenic transformation in normal rat kidney cells. Grp58 overexpression modulates STAT3 signaling in cancer...

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“…Several studies have shown that CLIC1 is expressed at a low level in normal gastric tissues and highly expressed in GC tissues [14-16]. It has also been found that the expression of CLIC1 in GC is closely related to the invasion and metastasis of lymph nodes and the infiltration of peripheral nerves, suggesting that CLIC1 is a potential tumor marker [7]. In this study, we successfully established a recombinant lentiviral expression vector targeting CLIC1 using RNAi, and then we established stable GC cell lines with low CLIC1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Chen et al [7] reported that the CLIC1 protein was over-expressed in human GC tissues, and its expression was correlated with lymph node metastasis, lymphatic vessel and nerve infiltration, pathological stage and survival rate. Zheng et al [8] confirmed that the over-expression of CLIC1 promoted the invasion and metastasis of GC cells.…”

Section: Introductionmentioning

confidence: 99%

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

Mao

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.

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Overexpression of CLIC1 in human gastric carcinoma and its clinicopathological significance

Cited by 104 publications

References 37 publications

Differential tissue-specific protein markers of vaginal carcinoma

Differential tissue-specific protein markers of vaginal carcinoma

Glucose‐regulated protein 58 modulates cell invasiveness and serves as a prognostic marker for cervical cancer

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

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