Skip to main content

Advertisement

SpringerLink
Log in

Activation of AKT is associated with metastasis of nasopharyngeal carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Although radiotherapy results of nasopharyngeal carcinoma (NPC) at an early stage are better than other tumors, there is still a portion of patients with NPC who die before 5 years after the treatment; the underlying mechanism remains to be further understood. This study aims to investigate the mechanism by which NPC cells escape from irradiation. Patients with NPC at stage I was included in this study. All the patients were treated with irradiation. NPC biopsies were obtained from each patient before and 1 week after the start of radiotherapy. Expression of AKT in NPC tissue was assessed by Western blotting. NPC cell line, SUNE-1 cells, was treated with irradiation. The levels of AKT in SUNE-1 cells were also assessed. The frequency of apoptotic SUNE-1 cells was evaluated by flow cytometry. The levels of AKT were markedly increased in NPC tissue after treatment with irradiation, which was significantly correlated with NPC metastasis and mortality. After irradiation, NPC cell line, SUNE-1 cells, expressed higher levels of AKT than control cells. The knockdown of AKT in SUNE-1 cells markedly increased apoptotic cell rate. Radiotherapy can increase the levels of AKT in NPC cells that are associated with NPC metastasis and increase in mortality.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Marcus KJ, Tishler RB. Head and neck carcinomas across the age spectrum: epidemiology, therapy, and late effects. Semin Radiat Oncol. 2010;20:52–7.

    Article  PubMed  Google Scholar 

  2. Agulnik M, Epstein JB. Nasopharyngeal carcinoma: current management, future directions and dental implications. Oral Oncol. 2008;44:617–27.

    Article  PubMed  Google Scholar 

  3. Sterzing F, Stoiber E, Nill S, Bauer H, Huber P, Debus J, et al. Intensity modulated radiotherapy (IMRT) in the treatment of children and adolescents—a single institution’s experience and a review of the literature. Radiat Oncol. 2009;4:37.

    Article  PubMed  Google Scholar 

  4. Loong HH, Ma BB, Chan AT. Update on the management and therapeutic monitoring of advanced nasopharyngeal cancer. Hematol Oncol Clin North Am. 2008;22:1267–78.

    Article  PubMed  Google Scholar 

  5. Koon HK, Chan PS, Wong RN-S, Wu ZG, Lung ML, Chang CK, et al. Targeted inhibition of the EGFR pathways enhances Zn-BC-AM PDT-induced apoptosis in well-differentiated nasopharyngeal carcinoma cells. J Cell Biochem. 2009;108:1356–63.

    Article  PubMed  CAS  Google Scholar 

  6. Freudlsperger C, Burnett JR, Friedman JA, Kannabiran VR, Chen Z, Van Waes C. EGFR-PI3K-AKT-mTOR signaling in head and neck squamous cell carcinomas: attractive targets for molecular-oriented therapy. Expert Opin Ther Targets. 2011;15(1):63–74.

    Article  PubMed  Google Scholar 

  7. Ming M, He YY. PTEN: new insights into its regulation and function in skin cancer. J Invest Dermatol. 2009;129:2109–12.

    Article  PubMed  CAS  Google Scholar 

  8. Kfir-Erenfeld S, Sionov RV, Spokoini R, Cohen O, Yefenof E. Protein kinase networks regulating glucocorticoid-induced apoptosis of hematopoietic cancer cells: fundamental aspects and practical considerations. Leuk Lymphoma. 2010;51:1968–2005.

    Article  PubMed  CAS  Google Scholar 

  9. Castaneda C, Cortes-Funes H, Gomez H, Ciruelos E. The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer. Cancer Meta Rev. 2010;29:751–9.

    Article  CAS  Google Scholar 

  10. Dent P, Yacoub A, Contessa J, Caron R, Amorino G, Valerie K, et al. Stress and radiation-induced activation of multiple intracellular signaling pathways1. Radiat Res. 2003;159:283–300.

    Article  PubMed  CAS  Google Scholar 

  11. Bussink J, van der Kogel AJ, Kaanders JH. Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol. 2008;9:288–96.

    Article  PubMed  CAS  Google Scholar 

  12. Eke I, Koch U, Hehlgans S, Sandfort V, Stanchi F, Zips D, et al. PINCH1 regulates Akt1 activation and enhances radioresistance by inhibiting PP1[alpha]. (Research article)(Report). J Clin Invest. 2010;120:2516–27.

    Article  PubMed  CAS  Google Scholar 

  13. Ayan I, Kaytan E, Ayan N. Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol. 2003;4:13–21.

    Article  PubMed  CAS  Google Scholar 

  14. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175–80.

    Article  PubMed  CAS  Google Scholar 

  15. Albert S, Serova M, Dreyer C, Sablin MP, Faivre S, Raymond E. New inhibitors of the mammalian target of rapamycin signaling pathway for cancer. Expert Opin Investig Drugs. 2010;19:919–30.

    Article  PubMed  CAS  Google Scholar 

  16. Jamil N, Howie S, Salter DM. Therapeutic molecular targets in human chondrosarcoma. Int J Exp Pathol. 2010;91:387–93.

    Article  PubMed  CAS  Google Scholar 

  17. Vens C, Begg AC. Targeting base excision repair as a sensitization strategy in radiotherapy. Semin Radiat Oncol. 2010;20:241–9.

    Article  PubMed  Google Scholar 

  18. Torres VE, Boletta A, Chapman A, Gattone V, Pei Y, Qian Q, et al. Prospects for mTOR inhibitor use in patients with polycystic kidney disease and hamartomatous diseases. Clin J Am Societ Nephrol. 2010;5:1312–29.

    Article  CAS  Google Scholar 

  19. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.

    Article  PubMed  CAS  Google Scholar 

  20. Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005;9:59–71.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interests

None.

Author information

Authors and Affiliations

  1. Department of Radiotherapy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China

    Ying Liu, Long-Hua Chen, Ya-Wei Yuan, Qi-Sheng Li, Ai-Ming Sun & Jian Guan

  2. Radiation Oncology, Southern Medical University, Guangdong, 510515, People’s Republic of China

    Long-Hua Chen

Authors
  1. Ying Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Long-Hua Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ya-Wei Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qi-Sheng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ai-Ming Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Long-Hua Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Y., Chen, LH., Yuan, YW. et al. Activation of AKT is associated with metastasis of nasopharyngeal carcinoma. Tumor Biol. 33, 241–245 (2012). https://doi.org/10.1007/s13277-011-0272-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-011-0272-4

Keywords

Search

Navigation