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Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer

Gallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognos... Full description

Journal Title: Journal of cancer research and clinical oncology November 2019, Vol.145(11), pp.2699-2711
Main Author: Golob-Schwarzl, Nicole
Other Authors: Wodlej, Christina , Kleinegger, Florian , Gogg-Kamerer, Margit , Birkl-Toeglhofer, Anna Maria , Petzold, Johannes , Aigelsreiter, Ariane , Thalhammer, Michael , Park, Young Nyun , Haybaeck, Johannes
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1432-1335 ; PMID: 31586263 Version:1 ; DOI: 10.1007/s00432-019-03030-x
Link: http://pubmed.gov/31586263
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recordid: medline31586263
title: Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer
format: Article
creator:
  • Golob-Schwarzl, Nicole
  • Wodlej, Christina
  • Kleinegger, Florian
  • Gogg-Kamerer, Margit
  • Birkl-Toeglhofer, Anna Maria
  • Petzold, Johannes
  • Aigelsreiter, Ariane
  • Thalhammer, Michael
  • Park, Young Nyun
  • Haybaeck, Johannes
subjects:
  • Biomarker
  • Eukaryotic Translation Initiation Factor 6
  • Gallbladder Cancer
  • Gene Expression Regulation, Neoplastic
  • Eukaryotic Initiation Factors -- Metabolism
  • Gallbladder Neoplasms -- Pathology
ispartof: Journal of cancer research and clinical oncology, November 2019, Vol.145(11), pp.2699-2711
description: Gallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers.... In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR). High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis. Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC.
language: eng
source:
identifier: E-ISSN: 1432-1335 ; PMID: 31586263 Version:1 ; DOI: 10.1007/s00432-019-03030-x
fulltext: fulltext
issn:
  • 14321335
  • 1432-1335
url: Link


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titleEukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer
creatorGolob-Schwarzl, Nicole ; Wodlej, Christina ; Kleinegger, Florian ; Gogg-Kamerer, Margit ; Birkl-Toeglhofer, Anna Maria ; Petzold, Johannes ; Aigelsreiter, Ariane ; Thalhammer, Michael ; Park, Young Nyun ; Haybaeck, Johannes
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subjectBiomarker ; Eukaryotic Translation Initiation Factor 6 ; Gallbladder Cancer ; Gene Expression Regulation, Neoplastic ; Eukaryotic Initiation Factors -- Metabolism ; Gallbladder Neoplasms -- Pathology
descriptionGallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers.... In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR). High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis. Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC.
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titleEukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer
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0Gallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers....
1In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR).
2High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis.
3Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC.
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titleEukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer
authorGolob-Schwarzl, Nicole ; Wodlej, Christina ; Kleinegger, Florian ; Gogg-Kamerer, Margit ; Birkl-Toeglhofer, Anna Maria ; Petzold, Johannes ; Aigelsreiter, Ariane ; Thalhammer, Michael ; Park, Young Nyun ; Haybaeck, Johannes
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abstractGallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers....
doi10.1007/s00432-019-03030-x
pmid31586263
orcididhttp://orcid.org/0000-0001-5518-3359
date2019-11-01