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Tumor Biology

, Volume 31, Issue 4, pp 359–361 | Cite as

Is Rab25 a tumor promoter or suppressor—context dependency on RCP status?

  • Bor Luen Tang
Research Commentary

Abstract

Conflicting reports in the literature suggest that Rab25 could either be a context dependent promoter or suppressor of tumorigenesis. We hypothesized that whether Rab25 acts as a promoter or suppressor in tumor progression depends on the expression status of its effector, the Rab coupling protein (RCP). An elevated expression of RCP resulting from genomic amplification may enhance Rab25’s tumor progression activity. Elevation of Rab25 alone may sequester endogenous RCP, and attenuates its activating effect on other oncogenic products, such as mutant Ras.

Keywords

Rab25 Rab coupling protein (RCP) Tumor promoter Tumor suppressor 

Notes

Acknowledgements

The author is grateful to the anonymous reviewers for their valuable suggestions, which improved the manuscript. He is supported by a grant from the Biomedical Research Council (BMRC) of the Agency for Science, Technology and Research (A*STAR) of Singapore (08/1/21/19/553), and declares no financial conflict of interest.

References

  1. 1.
    Cheng KW, Lahad JP, Gray JW, Mills GB. Emerging role of RAB GTPases in cancer and human disease. Cancer Res. 2005;65:2516–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Chia WJ, Tang BL. Emerging roles for Rab family GTPases in human cancer. Biochim Biophys Acta. 2009;1795:110–6.PubMedGoogle Scholar
  3. 3.
    Jing J, Prekeris R. Polarized endocytic transport: the roles of Rab11 and Rab11-FIPs in regulating cell polarity. Histol Histopathol. 2009;24:1171–80.PubMedGoogle Scholar
  4. 4.
    Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N, et al. The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med. 2004;10:1251–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Caswell PT, Spence HJ, Parsons M, White DP, Clark K, Cheng KW, et al. Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell. 2007;13:496–510.CrossRefPubMedGoogle Scholar
  6. 6.
    Cheng JM, Ding M, Aribi A, Shah P, Rao K. Loss of RAB25 expression in breast cancer. Int J Cancer. 2006;118:2957–64.CrossRefPubMedGoogle Scholar
  7. 7.
    Cheng JM, Volk L, Janaki DKM, Vyakaranam S, Ran S, Rao KA. 2009 Tumor suppressor function of Rab25 in triple negative breast cancer. Int J Cancer (in press).Google Scholar
  8. 8.
    Horgan CP, McCaffrey MW. The dynamic Rab11-FIPs. Biochem Soc Trans. 2009;37:1032–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Lindsay AJ, McCaffrey MW. The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane. J Cell Sci. 2004;117:4365–75.CrossRefPubMedGoogle Scholar
  10. 10.
    Caswell PT, Chan M, Lindsay AJ, McCaffrey MW, Boettiger D, Norman JC. Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J Cell Biol. 2008;183:143–55.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang J, Liu X, Datta A, Govindarajan K, Tam WL, Han J, et al. RCP is a human breast cancer-promoting gene with Ras-activating function. J Clin Invest. 2009;119:2171–83.PubMedGoogle Scholar
  12. 12.
    Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, et al. Mutant p53 drives invasion by promoting integrin recycling. Cell. 2009;139:1327–41.CrossRefPubMedGoogle Scholar
  13. 13.
    Finlan LE, Hupp TR. p63: the phantom of the tumor suppressor. Cell Cycle. 2007;6:1062–71.PubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  1. 1.Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health ServiceNational University of SingaporeSingaporeSingapore

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