Role of V-ATPases in solid tumors: Importance of the subunit C (Review)

  • Authors:
    • Mario Pérez-Sayáns
    • Abel García-García
    • María Dolores Reboiras-López
    • Pilar Gándara-Vila
  • Corresponding author:
  • View Affiliations

  • Published online on: Monday, June 1, 2009
  • Pages: 1513-1520 DOI: 10.3892/ijo_00000280

Abstract

Acidity is one of the main characteristics of OSCC (oral squamous cell carcinoma) as a solid tumor. The V-ATPase is the primary regulator of the tumor microenvironment, by means of proton extrusion to the extracellular medium. The decrease in extracellular pH confers the cells a resistant, highly invasive and metastatic phenotype. However, the acid medium confers an optimum pH to the degradative enzymes (such as proteases and MMPs) for their proper functioning. The C subunit (ATP6V1C) of V1 intra-membrane domain of the V-ATPase, is primarily responsible for its enzymatic function, through the control of a reversible dissociation of V0 and V1 domains. In this review, we describe the importance of V-ATPases in the control of tumor microenvironment, the potential strategies as protein targeting to improve the effectiveness of drug treatment and the role of the C subunit as the primarily responsible of the enzymatic control. The inhibition of the V-ATPase activity through PPIs (proton inhibitors) seems to reduce the destructive and metastatic capacity in tumors, such as hepatocellular carcinoma. Nevertheless, none of these inhibitors was proven to be useful in OSCC; therefore, it is highly important to carry out further studies in order to develop specific inhibitors of the C subunit, to control the devastating effects of OSCC.
Journal Cover

June 2009
Volume 34 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
2014 I.F. (Expected) ≥ 3.310 Ranked #30/202 Oncology
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APA
Pérez-Sayáns, M., García-García, A., Reboiras-López, M.D., & Gándara-Vila, P. (2009). Role of V-ATPases in solid tumors: Importance of the subunit C (Review). International Journal of Oncology, 34, 1513-1520. http://dx.doi.org/10.3892/ijo_00000280
MLA
Pérez-Sayáns, M., García-García, A., Reboiras-López, M. D., Gándara-Vila, P."Role of V-ATPases in solid tumors: Importance of the subunit C (Review)". International Journal of Oncology 34.6 (2009): 1513-1520.
Chicago
Pérez-Sayáns, M., García-García, A., Reboiras-López, M. D., Gándara-Vila, P."Role of V-ATPases in solid tumors: Importance of the subunit C (Review)". International Journal of Oncology 34, no. 6 (2009): 1513-1520. http://dx.doi.org/10.3892/ijo_00000280