The Secretory Small GTPase Rab27B As a Marker for Breast Cancer Progression

Overview

Journal Oncotarget

Specialty Oncology

Date 2011 Feb 10

PMID 21304180

Citations 26

Authors

An Hendrix

Geert Braems

Marc Bracke

Miguel C Seabra

William A Gahl

Olivier de Wever

Wendy Westbroek

Affiliations

Soon will be listed here.

Abstract

In contemporary oncology practice, an urgent need remains to refine the prognostic assessment of breast cancer. It is still difficult to identify patients with early breast cancer who are likely to benefit from adjuvant chemotherapy. Although invasion of cancer cells is the main prognostic denominator in tumor malignancy, our molecular understanding and diagnosis are often inadequate to cope with this activity. Therefore, deciphering molecular pathways of how tumors invade and metastasize may help in the identification of a useful prognostic marker. We recently discovered that the secretory small GTPase Rab27B, a regulator of vesicle exocytosis, delivers proinvasive signals for increased invasiveness, tumor size, and metastasis of various estrogen receptor (ER)-positive breast cancer cell lines, both in vitro and in vivo. In human breast cancer specimens, the presence of Rab27B protein proved to be associated with a low degree of differentiation and the presence of lymph node metastasis in ER-positive breast cancer.

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References

Westbroek W, Lambert J, De Schepper S, Kleta R, Van Den Bossche K, Seabra M . Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts. Pigment Cell Res. 2004; 17(5):498-505. DOI: 10.1111/j.1600-0749.2004.00173.x. View

Jordens I, Westbroek W, Marsman M, Rocha N, Mommaas M, Huizing M . Rab7 and Rab27a control two motor protein activities involved in melanosomal transport. Pigment Cell Res. 2006; 19(5):412-23. DOI: 10.1111/j.1600-0749.2006.00329.x. View

Wright P, May F, Darby S, Saif R, Lennard T, Westley B . Estrogen regulates vesicle trafficking gene expression in EFF-3, EFM-19 and MCF-7 breast cancer cells. Int J Clin Exp Pathol. 2009; 2(5):463-75. PMC: 2655148. View

Chen D, Guo J, Miki T, Tachibana M, Gahl W . Molecular cloning and characterization of rab27a and rab27b, novel human rab proteins shared by melanocytes and platelets. Biochem Mol Med. 1997; 60(1):27-37. DOI: 10.1006/bmme.1996.2559. View

Fukuda M . Regulation of secretory vesicle traffic by Rab small GTPases. Cell Mol Life Sci. 2008; 65(18):2801-13. PMC: 11131888. DOI: 10.1007/s00018-008-8351-4. View

Westbroek W, Tuchman M, Tinloy B, de Wever O, Vilboux T, Hertz J . A novel missense mutation (G43S) in the switch I region of Rab27A causing Griscelli syndrome. Mol Genet Metab. 2008; 94(2):248-54. PMC: 2430933. DOI: 10.1016/j.ymgme.2008.02.009. View

Wang J, Wang F, Zhang Q, Shen Z, Shao Z . Enhanced expression of Rab27A gene by breast cancer cells promoting invasiveness and the metastasis potential by secretion of insulin-like growth factor-II. Mol Cancer Res. 2008; 6(3):372-82. DOI: 10.1158/1541-7786.MCR-07-0162. View

Barral D, Ramalho J, Anders R, Hume A, Knapton H, Tolmachova T . Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome. J Clin Invest. 2002; 110(2):247-57. PMC: 151050. DOI: 10.1172/JCI15058. View

Ostrowski M, Carmo N, Krumeich S, Fanget I, Raposo G, Savina A . Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2009; 12(1):19-30. DOI: 10.1038/ncb2000. View

10.

Cheng J, Volk L, Janaki D, Vyakaranam S, Ran S, Rao K . Tumor suppressor function of Rab25 in triple-negative breast cancer. Int J Cancer. 2009; 126(12):2799-812. DOI: 10.1002/ijc.24900. View

11.

Westbroek W, Lambert J, Bahadoran P, Busca R, Herteleer M, Smit N . Interactions of human Myosin Va isoforms, endogenously expressed in human melanocytes, are tightly regulated by the tail domain. J Invest Dermatol. 2003; 120(3):465-75. DOI: 10.1046/j.1523-1747.2003.12068.x. View

12.

Burgoyne R, Morgan A . Secretory granule exocytosis. Physiol Rev. 2003; 83(2):581-632. DOI: 10.1152/physrev.00031.2002. View

13.

Pagani O, Price K, Gelber R, Castiglione-Gertsch M, Holmberg S, Lindtner J . Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century. Breast Cancer Res Treat. 2009; 117(2):319-24. PMC: 3589101. DOI: 10.1007/s10549-008-0282-0. View

14.

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

15.

Cheng K, Lahad J, Kuo W, Lapuk A, Yamada K, Auersperg N . The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med. 2004; 10(11):1251-6. DOI: 10.1038/nm1125. View

16.

Hendrix A, Maynard D, Pauwels P, Braems G, Denys H, Van den Broecke R . Effect of the secretory small GTPase Rab27B on breast cancer growth, invasion, and metastasis. J Natl Cancer Inst. 2010; 102(12):866-80. PMC: 2886092. DOI: 10.1093/jnci/djq153. View

17.

Cheng J, Ding M, Aribi A, Shah P, Rao K . Loss of RAB25 expression in breast cancer. Int J Cancer. 2006; 118(12):2957-64. DOI: 10.1002/ijc.21739. View

18.

Stenmark H . Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 2009; 10(8):513-25. DOI: 10.1038/nrm2728. View

19.

Johnson J, Brzezinska A, Tolmachova T, Munafo D, Ellis B, Seabra M . Rab27a and Rab27b regulate neutrophil azurophilic granule exocytosis and NADPH oxidase activity by independent mechanisms. Traffic. 2009; 11(4):533-47. PMC: 2937183. DOI: 10.1111/j.1600-0854.2009.01029.x. View

20.

Tolmachova T, Abrink M, Futter C, Authi K, Seabra M . Rab27b regulates number and secretion of platelet dense granules. Proc Natl Acad Sci U S A. 2007; 104(14):5872-7. PMC: 1831675. DOI: 10.1073/pnas.0609879104. View