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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
January-2018 Volume 39 Issue 1

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
January-2018 Volume 39 Issue 1

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 Open Access

EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway

  • Authors:
    • Rui Huang
    • Huimin Liu
    • Yiran Chen
    • Yanjie He
    • Qian Kang
    • Sanfang Tu
    • Yingzhi He
    • Xuan Zhou
    • Lei Wang
    • Jilong Yang
    • Anqin Wu
    • Yuhua Li
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 119-128
    |
    Published online on: November 20, 2017
       https://doi.org/10.3892/or.2017.6102
  • 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

Although the introduction of tyrosine kinase inhibitors greatly improved the survival of patients with chronic myeloid leukemia (CML), drug resistance remains a problem. Thus, mechanism-based novel therapeutic targets warrant exploration. Recently, epidermal growth factor receptor kinase substrate 8 (EPS8), which has been identified as an oncogene and plays an important role in a broad spectrum of solid tumours, was reported to be related to poor prognosis or chemoresistance in acute leukemia patients. However, its role in CML remains unclear. In the present study, using q-RT‑PCR, we demonstrated that CML patients expressed a higher level of EPS8 mRNA in bone marrow mononuclear cells than healthy controls. Then, to determine the effect of EPS8 on the biological functions of CML cells, EPS8 expression was knocked down in the human CML cell line K562. Reduced proliferation, increased apoptosis, impaired adhesion and migration were observed in K562 cells after EPS8 silencing. Notably, attenuation of EPS8 increased chemosensitivity both in imatinib-sensitive K562 cells and in the imatinib-resistant murine BCR-ABL+ 32D-p210BCR/ABL-T315I cells. Mechanistically, knockdown of EPS8 downregulated p-BCR/ABL and its downstream AKT/mTOR signalling pathway. Finally, knockdown of EPS8 attenuated K562 cell proliferation in BALB/c nude mice. These data indicated that EPS8 regulated the proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Targeting EPS8 alone or combined with a tyrosine kinase inhibitor may be a promising alternative therapeutic strategy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Huang R, Kang Q, Liu H and Li Y: New insights into the molecular resistance mechanisms of chronic myeloid leukemia. Curr Cancer Drug Targets. 16:323–345. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, et al IRIS Investigators, : Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 355:2408–2417. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Hochhaus A, O'Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L, Goldman JM, Müller MC, Radich JP, Rudoltz M, et al IRIS Investigators, : Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 23:1054–1061. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN and Sawyers CL: Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 293:876–880. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Thomas J, Wang L, Clark RE and Pirmohamed M: Active transport of imatinib into and out of cells: Implications for drug resistance. Blood. 104:3739–3745. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Li YH, Xue TY, He YZ and Du JW: Novel oncoprotein EPS8: A new target for anticancer therapy. Future Oncol. 9:1587–1594. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Maa MC, Hsieh CY and Leu TH: Overexpression of p97Eps8 leads to cellular transformation: Implication of pleckstrin homology domain in p97Eps8-mediated ERK activation. Oncogene. 20:106–112. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Chen C, Liang Z, Huang W, Li X, Zhou F, Hu X, Han M, Ding X and Xiang S: Eps8 regulates cellular proliferation and migration of breast cancer. Int J Oncol. 46:205–214. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Chen H, Wu X, Pan ZK and Huang S: Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis. Cancer Res. 70:9979–9990. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Ding X, Zhou F, Wang F, Yang Z, Zhou C, Zhou J, Zhang B, Yang J, Wang G, Wei Z, et al: Eps8 promotes cellular growth of human malignant gliomas. Oncol Rep. 29:697–703. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Schoenherr C, Serrels B, Proby C, Cunningham DL, Findlay JE, Baillie GS, Heath JK and Frame MC: Eps8 controls Src- and FAK-dependent phenotypes in squamous carcinoma cells. J Cell Sci. 127:5303–5316. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Sun J, Jin LY, Wang HY, Zhou JQ, Li YJ, He YZ and Li YH: Correlation of Eps8 with proliferation, metastasis and prognosis of malignant tumors. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 21:493–497. 2013.(In Chinese). PubMed/NCBI

13 

Kang H, Wilson CS, Harvey RC, Chen IM, Murphy MH, Atlas SR, Bedrick EJ, Devidas M, Carroll AJ, Robinson BW, et al: Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: A Children's Oncology Group study. Blood. 119:1872–1881. 2012. View Article : Google Scholar : PubMed/NCBI

14 

He YZ, Liang Z, Wu MR, Wen Q, Deng L, Song CY, Wu BY, Tu SF, Huang R and Li YH: Overexpression of EPS8 is associated with poor prognosis in patients with acute lymphoblastic leukemia. Leuk Res. 39:575–581. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Wang L, Cai SH, Xiong WY, He YJ, Deng L and Li YH: Real-time quantitative polymerase chain reaction assay for detecting the eps8 gene in acute myeloid leukemia. Clin Lab. 59:1261–1269. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Radich JP, Dai H, Mao M, Oehler V, Schelter J, Druker B, Sawyers C, Shah N, Stock W, Willman CL, et al: Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 103:pp. 2794–2799. 2006; View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Cross DA, Alessi DR, Cohen P, Andjelkovich M and Hemmings BA: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378:785–789. 1995. View Article : Google Scholar : PubMed/NCBI

19 

Xu M, Shorts-Cary L, Knox AJ, Kleinsmidt-DeMasters B, Lillehei K and Wierman ME: Epidermal growth factor receptor pathway substrate 8 is overexpressed in human pituitary tumors: Role in proliferation and survival. Endocrinology. 150:2064–2071. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Wang H, Patel V, Miyazaki H, Gutkind JS and Yeudall WA: Role for EPS8 in squamous carcinogenesis. Carcinogenesis. 30:165–174. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Capala ME, Vellenga E and Schuringa JJ: ELMO1 is upregulated in AML CD34+ stem/progenitor cells, mediates chemotaxis and predicts poor prognosis in normal karyotype AML. PLoS One. 9:e1115682014. View Article : Google Scholar : PubMed/NCBI

22 

Wang H, Teh MT, Ji Y, Patel V, Firouzabadian S, Patel AA, Gutkind JS and Yeudall WA: EPS8 upregulates FOXM1 expression, enhancing cell growth and motility. Carcinogenesis. 31:1132–1141. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Yap LF, Jenei V, Robinson CM, Moutasim K, Benn TM, Threadgold SP, Lopes V, Wei W, Thomas GJ and Paterson IC: Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation. Oncogene. 28:2524–2534. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Gorsic LK, Stark AL, Wheeler HE, Wong SS, Im HK and Dolan ME: EPS8 inhibition increases cisplatin sensitivity in lung cancer cells. PLoS One. 8:e822202013. View Article : Google Scholar : PubMed/NCBI

25 

Chen YJ, Shen MR, Chen YJ, Maa MC and Leu TH: Eps8 decreases chemosensitivity and affects survival of cervical cancer patients. Mol Cancer Ther. 7:1376–1385. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Maa MC, Lee JC, Chen YJ, Chen YJ, Lee YC, Wang ST, Huang CC, Chow NH and Leu TH: Eps8 facilitates cellular growth and motility of colon cancer cells by increasing the expression and activity of focal adhesion kinase. J Biol Chem. 282:19399–19409. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Reckel S, Hamelin R, Georgeon S, Armand F, Jolliet Q, Chiappe D, Moniatte M and Hantschel O: Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics. Leukemia. 31:1502–1512. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huang R, Liu H, Chen Y, He Y, Kang Q, Tu S, He Y, Zhou X, Wang L, Yang J, Yang J, et al: EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Oncol Rep 39: 119-128, 2018.
APA
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S. ... Li, Y. (2018). EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Oncology Reports, 39, 119-128. https://doi.org/10.3892/or.2017.6102
MLA
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S., He, Y., Zhou, X., Wang, L., Yang, J., Wu, A., Li, Y."EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway". Oncology Reports 39.1 (2018): 119-128.
Chicago
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S., He, Y., Zhou, X., Wang, L., Yang, J., Wu, A., Li, Y."EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway". Oncology Reports 39, no. 1 (2018): 119-128. https://doi.org/10.3892/or.2017.6102
Copy and paste a formatted citation
x
Spandidos Publications style
Huang R, Liu H, Chen Y, He Y, Kang Q, Tu S, He Y, Zhou X, Wang L, Yang J, Yang J, et al: EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Oncol Rep 39: 119-128, 2018.
APA
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S. ... Li, Y. (2018). EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway. Oncology Reports, 39, 119-128. https://doi.org/10.3892/or.2017.6102
MLA
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S., He, Y., Zhou, X., Wang, L., Yang, J., Wu, A., Li, Y."EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway". Oncology Reports 39.1 (2018): 119-128.
Chicago
Huang, R., Liu, H., Chen, Y., He, Y., Kang, Q., Tu, S., He, Y., Zhou, X., Wang, L., Yang, J., Wu, A., Li, Y."EPS8 regulates proliferation, apoptosis and chemosensitivity in BCR-ABL positive cells via the BCR-ABL/PI3K/AKT/mTOR pathway". Oncology Reports 39, no. 1 (2018): 119-128. https://doi.org/10.3892/or.2017.6102
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