Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2019 Volume 20 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2019 Volume 20 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance

  • Authors:
    • Jun Cao
    • Chi Zhang
    • Guo‑Qing Jiang
    • Sheng‑Jie Jin
    • Zhi‑Hui Gao
    • Qian Wang
    • De‑Cai Yu
    • Ai‑Wu Ke
    • Yi‑Qun Fan
    • Da‑Wei Li
    • Ao‑Qing Wang
    • Dou‑Sheng Bai
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China, Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China, Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China, Liver Cancer Institute, Ministry of Education, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Shanghai 200032, P.R. China, Department of Surgery, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
  • Pages: 1915-1924
    |
    Published online on: June 19, 2019
       https://doi.org/10.3892/mmr.2019.10399
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Kidney‑type glutaminase (GLS1) plays a significant role in tumor metabolism. Our recent studies demonstrated that GLS1 was aberrantly expressed in hepatocellular carcinoma (HCC) and facilitated tumor progression. However, the roles of GLS1 in intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Thus, the aim of this study was to evaluate the expression and clinical significance of GLS1 in ICC. For this purpose, combined data from the Oncomine database with those of immunohistochemistry were used to determine the expression levels of GLS1 in cancerous and non‑cancerous tissues. Second, a wound‑healing assay and Transwell assay were used to observe the effects of the knockdown and overexpression of GLS1 on the invasion and migration of ICC cells. We examined the associations between the expression of GLS1 and epithelial‑mesenchymal transition (EMT)‑related markers by western blot analysis. Finally, we examined the associations between GLS1 levels and clinicopathological factors or patient prognosis. The results revealed that GLS1 was overexpressed in different digestive system tumors, including ICC, and that GLS1 expression in ICC tissue was higher than that in peritumoral tissue. The overexpression of GLS1 in RBE cells induced metastasis and invasion. Moreover, the EMT‑related markers, E‑cadherin and Vimentin, were regulated by GLS1 in ICC cells. By contrast, the knockdown of GLS1 expression in QBC939 cells yielded opposite results. Clinically, a high expression of GLS1 in ICC samples negatively correlated with E‑cadherin expression and positively correlated with Vimentin expression. GLS1 protein expression was associated with tumor differentiation (P=0.001) and lymphatic metastasis (P=0.029). Importantly, patients with a high GLS1 expression had a poorer overall survival (OS) and a shorter time to recurrence than patients with a low GLS1 expression. Multivariate analysis indicated that GLS1 expression was an independent prognostic indicator. On the whole, the findings of this study demonstrated that GLS1 is an independent prognostic biomarker of ICC. GLS1 facilitates ICC progression and may thus prove to be a therapeutic target in ICC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Bartella I and Dufour JF: Clinical diagnosis and staging of intrahepatic cholangiocarcinoma. J Gastrointestin Liver Dis. 24:481–489. 2015.PubMed/NCBI

2 

Guo LH and Xu HX: Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Controversy over the ASSLD Guideline. Biomed Res Int. 2015:3491722015. View Article : Google Scholar : PubMed/NCBI

3 

Guro H, Kim JW, Choi Y, Cho JY, Yoon YS and Han HS: Multidisciplinary management of intrahepatic cholangiocarcinoma: Current approaches. Surg Oncol. 26:146–152. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Yoh T, Hatano E, Nishio T, Seo S, Taura K, Yasuchika K, Okajima H, Kaido T and Uemoto S: Significant improvement in outcomes of patients with intrahepatic cholangiocarcinoma after surgery. World J Surg. 40:2229–2236. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G and Iacono C: Intrahepatic cholangiocarcinoma: Prognostic factors after surgical resection. World J Surg. 33:1247–1254. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Yu D, Shi X, Meng G, Chen J, Yan C, Jiang Y, Wei J and Ding Y: Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and prognosis of hepatocellular carcinoma. Oncotarget. 6:7619–7631. 2015.PubMed/NCBI

8 

Qie S, Chu C, Li W, Wang C and Sang N: ErbB2 activation upregulates glutaminase 1 expression which promotes breast cancer cell proliferation. J Cell Biochem. 115:498–509. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Huang F, Zhang Q, Ma H, Lv Q and Zhang T: Expression of glutaminase is upregulated in colorectal cancer and of clinical significance. Int J Clin Exp Pathol. 7:1093–1100. 2014.PubMed/NCBI

10 

Huang F, Wang BR and Wang YG: Role of autophagy in tumorigenesis, metastasis, targeted therapy and drug resistance of hepatocellular carcinoma. World J Gastroenterol. 24:4643–4651. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Klymkowsky MW: Beta-catenin and its regulatory network. Hum Pathol. 36:225–227. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Lee SY, Jeon HM, Ju MK, Jeong EK, Kim CH, Park HG, Han SI and Kang HS: Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch. Oncotarget. 7:7925–7939. 2016.PubMed/NCBI

13 

Bai DS, Dai Z, Zhou J, Liu YK, Qiu SJ, Tan CJ, Shi YH, Huang C, Wang Z, He YF and Fan J: Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology. 49:460–470. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Roessler S, Jia HL, Budhu A, Forgues M, Ye QH, Lee JS, Thorgeirsson SS, Sun Z, Tang ZY, Qin LX and Wang XW: A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients. Cancer Res. 70:10202–10212. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Cui J, Chen Y, Chou WC, Sun L, Chen L, Suo J, Ni Z, Zhang M, Kong X, Hoffman LL, et al: An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer. Nucleic Acids Res. 39:1197–1207. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Skrzypczak M, Goryca K, Rubel T, Paziewska A, Mikula M, Jarosz D, Pachlewski J, Oledzki J and Ostrowski J: Modeling oncogenic signaling in colon tumors by multidirectional analyses of microarray data directed for maximization of analytical reliability. PLoS One. 5(pii): e130912010. View Article : Google Scholar : PubMed/NCBI

17 

Zhao Y, Butler EB and Tan M: Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis. 4:e5322013. View Article : Google Scholar : PubMed/NCBI

18 

Abu Aboud O, Habib SL, Trott J, Stewart B, Liang S, Chaudhari AJ, Sutcliffe J and Weiss RH: Glutamine addiction in kidney cancer suppresses oxidative stress and can Be exploited for real-time imaging. Cancer Res. 77:6746–6758. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Pan T, Gao L, Wu G, Shen G, Xie S, Wen H, Yang J, Zhou Y, Tu Z and Qian W: Elevated expression of glutaminase confers glucose utilization via glutaminolysis in prostate cancer. Biochem Biophys Res Commun. 456:452–458. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Krebs AM, Mitschke J, Lasierra Losada M, Schmalhofer O, Boerries M, Busch H, Boettcher M, Mougiakakos D, Reichardt W, Bronsert P, et al: The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol. 19:518–529. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Qureshi R, Arora H and Rizvi MA: EMT in cervical cancer: Its role in tumour progression and response to therapy. Cancer Lett. 356:321–331. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Terry S, Savagner P, Ortiz-Cuaran S, Mahjoubi L, Saintigny P, Thiery JP and Chouaib S: New insights into the role of EMT in tumor immune escape. Mol Oncol. 11:824–846. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Ulanet DB, Couto K, Jha A, Choe S, Wang A, Woo HK, Steadman M, DeLaBarre B, Gross S, Driggers E, et al: Mesenchymal phenotype predisposes lung cancer cells to impaired proliferation and redox stress in response to glutaminase inhibition. PLoS One. 9:e1151442014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cao J, Zhang C, Jiang GQ, Jin SJ, Gao ZH, Wang Q, Yu DC, Ke AW, Fan YQ, Li DW, Li DW, et al: Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance. Mol Med Rep 20: 1915-1924, 2019.
APA
Cao, J., Zhang, C., Jiang, G., Jin, S., Gao, Z., Wang, Q. ... Bai, D. (2019). Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance. Molecular Medicine Reports, 20, 1915-1924. https://doi.org/10.3892/mmr.2019.10399
MLA
Cao, J., Zhang, C., Jiang, G., Jin, S., Gao, Z., Wang, Q., Yu, D., Ke, A., Fan, Y., Li, D., Wang, A., Bai, D."Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance". Molecular Medicine Reports 20.2 (2019): 1915-1924.
Chicago
Cao, J., Zhang, C., Jiang, G., Jin, S., Gao, Z., Wang, Q., Yu, D., Ke, A., Fan, Y., Li, D., Wang, A., Bai, D."Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance". Molecular Medicine Reports 20, no. 2 (2019): 1915-1924. https://doi.org/10.3892/mmr.2019.10399
Copy and paste a formatted citation
x
Spandidos Publications style
Cao J, Zhang C, Jiang GQ, Jin SJ, Gao ZH, Wang Q, Yu DC, Ke AW, Fan YQ, Li DW, Li DW, et al: Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance. Mol Med Rep 20: 1915-1924, 2019.
APA
Cao, J., Zhang, C., Jiang, G., Jin, S., Gao, Z., Wang, Q. ... Bai, D. (2019). Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance. Molecular Medicine Reports, 20, 1915-1924. https://doi.org/10.3892/mmr.2019.10399
MLA
Cao, J., Zhang, C., Jiang, G., Jin, S., Gao, Z., Wang, Q., Yu, D., Ke, A., Fan, Y., Li, D., Wang, A., Bai, D."Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance". Molecular Medicine Reports 20.2 (2019): 1915-1924.
Chicago
Cao, J., Zhang, C., Jiang, G., Jin, S., Gao, Z., Wang, Q., Yu, D., Ke, A., Fan, Y., Li, D., Wang, A., Bai, D."Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance". Molecular Medicine Reports 20, no. 2 (2019): 1915-1924. https://doi.org/10.3892/mmr.2019.10399
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team