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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
April-2015 Volume 46 Issue 4

Full Size Image

Cover Legend PDF

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
April-2015 Volume 46 Issue 4

Full Size Image

Cover Legend PDF

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

Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer

  • Authors:
    • Masayoshi Toge
    • Satoru Yokoyama
    • Shinichiro Kato
    • Hiroaki Sakurai
    • Kazutaka Senda
    • Yoshinori Doki
    • Yoshihiro Hayakawa
    • Naoki Yoshimura
    • Ikuo Saiki
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic and Cardiovascular Surgery, University of Toyama, Toyama 930-0194, Japan, Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan
  • Pages: 1844-1848
    |
    Published online on: January 30, 2015
       https://doi.org/10.3892/ijo.2015.2861
  • 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

Non-small cell lung cancer (NSCLC) is one of the leading causes of death in all lung cancer patients due to its metastatic spread. Even though cisplatin treatment after surgical resection of the primary tumor has been established as a standard chemotherapy for residual disease including metastatic spread, NSCLC often acquires a resistance against chemotherapy, and metastatic disease is often observed. Amongst many potential mechanisms, epithelial-to-mesenchymal transition (EMT) has been considered as an important process in acquiring both metastatic spread and chemo-resistance of NSCLC. In this study, we identified MCL-1 as a critical molecule for chemo-resistance in A549 cells associated with TGF-β-induced EMT. Importantly, downregulation of MCL-1 by siRNA or inhibition of MCL-1 with pan-BCL2 inhibitor to inhibit MCL-1 was able to overcome the EMT-associated chemo-resistance in A549 cells. Collectively, MCL-1 can be a new therapeutic target for overcoming EMT-associated chemo-resistance in NSCLC patients in the context of post-operative chemotherapies.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Ohe Y, Ohashi Y, Kubota K, et al: Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 18:317–323. 2007. View Article : Google Scholar

2 

Groome PA, Bolejack V, Crowley JJ, et al: The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2:694–705. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Ginsberg RJ and Rubinstein LV: Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg. 60:613–622. 1995. View Article : Google Scholar

4 

Carr SR, Schuchert MJ, Pennathur A, et al: Impact of tumor size on outcomes after anatomic lung resection for stage 1A non-small cell lung cancer based on the current staging system. J Thorac Cardiovasc Surg. 143:390–397. 2012. View Article : Google Scholar

5 

Douillard JY, Rosell R, De Lena M, et al: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 7:719–727. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP and Vansteenkiste J: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 350:351–360. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Winton T, Livingston R, Johnson D, et al: Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 352:2589–2597. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Fidler IJ: The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 3:453–458. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2012. View Article : Google Scholar

10 

Ledford H: Cancer theory faces doubts. Nature. 472:2732011. View Article : Google Scholar : PubMed/NCBI

11 

Thiery JP: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2:442–454. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Tsai JH, Donaher JL, Murphy DA, Chau S and Yang J: Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell. 22:725–736. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Rho JK, Choi YJ, Lee JK, et al: Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer. 63:219–226. 2009. View Article : Google Scholar

14 

Shintani Y, Okimura A, Sato K, et al: Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell lung cancer. Ann Thorac Surg. 92:1794–1804. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Haq R, Yokoyama S, Hawryluk EB, et al: BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. Proc Natl Acad Sci USA. 110:4321–4326. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Thomson S, Buck E, Petti F, et al: Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition. Cancer Res. 65:9455–9462. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Kato S, Hayakawa Y, Sakurai H, Saiki I and Yokoyama S: Mesenchymal-transitioned cancer cells instigate the invasion of epithelial cancer cells through secretion of WNT3 and WNT5B. Cancer Sci. 105:281–289. 2014. View Article : Google Scholar

18 

Kin R, Kato S, Kaneto N, et al: Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epithelial-to-mesenchymal transition in the A549 lung cancer cell line. Int J Oncol. 43:1901–1906. 2013.PubMed/NCBI

19 

Li J, Viallet J and Haura EB: A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatin-induced apoptosis in non-small cell lung cancer cells. Cancer Chemother Pharmacol. 61:525–534. 2008. View Article : Google Scholar

20 

Henson ES, Gibson EM, Villanueva J, Bristow NA, Haney N and Gibson SB: Increased expression of Mcl-1 is responsible for the blockage of TRAIL-induced apoptosis mediated by EGF/ErbB1 signaling pathway. J Cell Biochem. 89:1177–1192. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Liu H, Zhang T, Wu B, Huang J, Zhou Y and Zhu J: Chronic exposure to exogenous matrilysin induces chemoresistance and enhances Bcl-2 expression in A549 lung adenocarcinoma cells. Mol Biol Rep. 36:2099–2109. 2009. View Article : Google Scholar

22 

Nishioka T, Luo LY, Shen L, et al: Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability. Br J Cancer. 110:1785–1792. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Leu CM, Chang C and Hu C: Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway. Oncogene. 19:1665–1675. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Lu Z, Ghosh S, Wang Z and Hunter T: Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell. 4:499–515. 2003. View Article : Google Scholar

25 

Hu P, Chu GC, Zhu G, et al: Multiplexed quantum dot labeling of activated c-Met signaling in castration-resistant human prostate cancer. PLoS One. 6:e286702011. View Article : Google Scholar : PubMed/NCBI

26 

Schulze-Bergkamen H, Brenner D, Krueger A, et al: Hepatocyte growth factor induces Mcl-1 in primary human hepatocytes and inhibits CD95-mediated apoptosis via Akt. Hepatology. 39:645–654. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Jin HO, Hong SE, Woo SH, et al: Silencing of Twist1 sensitizes NSCLC cells to cisplatin via AMPK-activated mTOR inhibition. Cell Death Dis. 3:e3192012. View Article : Google Scholar : PubMed/NCBI

28 

Sanchez-Tillo E, Fanlo L, Siles L, et al: The EMT activator ZEB1 promotes tumor growth and determines differential response to chemotherapy in mantle cell lymphoma. Cell Death Differ. 21:247–257. 2014. View Article : Google Scholar :

29 

Li Z, Zhao J, Du Y, et al: Downregulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci USA. 105:162–167. 2008. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Toge M, Yokoyama S, Kato S, Sakurai H, Senda K, Doki Y, Hayakawa Y, Yoshimura N and Saiki I: Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer. Int J Oncol 46: 1844-1848, 2015.
APA
Toge, M., Yokoyama, S., Kato, S., Sakurai, H., Senda, K., Doki, Y. ... Saiki, I. (2015). Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer. International Journal of Oncology, 46, 1844-1848. https://doi.org/10.3892/ijo.2015.2861
MLA
Toge, M., Yokoyama, S., Kato, S., Sakurai, H., Senda, K., Doki, Y., Hayakawa, Y., Yoshimura, N., Saiki, I."Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer". International Journal of Oncology 46.4 (2015): 1844-1848.
Chicago
Toge, M., Yokoyama, S., Kato, S., Sakurai, H., Senda, K., Doki, Y., Hayakawa, Y., Yoshimura, N., Saiki, I."Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer". International Journal of Oncology 46, no. 4 (2015): 1844-1848. https://doi.org/10.3892/ijo.2015.2861
Copy and paste a formatted citation
x
Spandidos Publications style
Toge M, Yokoyama S, Kato S, Sakurai H, Senda K, Doki Y, Hayakawa Y, Yoshimura N and Saiki I: Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer. Int J Oncol 46: 1844-1848, 2015.
APA
Toge, M., Yokoyama, S., Kato, S., Sakurai, H., Senda, K., Doki, Y. ... Saiki, I. (2015). Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer. International Journal of Oncology, 46, 1844-1848. https://doi.org/10.3892/ijo.2015.2861
MLA
Toge, M., Yokoyama, S., Kato, S., Sakurai, H., Senda, K., Doki, Y., Hayakawa, Y., Yoshimura, N., Saiki, I."Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer". International Journal of Oncology 46.4 (2015): 1844-1848.
Chicago
Toge, M., Yokoyama, S., Kato, S., Sakurai, H., Senda, K., Doki, Y., Hayakawa, Y., Yoshimura, N., Saiki, I."Critical contribution of MCL-1 in EMT-associated chemo-resistance in A549 non-small cell lung cancer". International Journal of Oncology 46, no. 4 (2015): 1844-1848. https://doi.org/10.3892/ijo.2015.2861
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