Document Detail

V-ATPase expression and activity is required for Rab27B-dependent invasive growth and metastasis of breast cancer.
MedLine Citation:
PMID:  23390068     Owner:  NLM     Status:  Publisher    
The secretory Rab27B small GTPase promotes invasive growth and metastasis in estrogen receptor (ER)α-positive breast cancer cells by orchestrating the peripheral targeting of vesicles secreting pro-invasive growth regulators. Increased Rab27B expression is associated with poor prognosis in breast cancer patients. The molecular mechanisms of peripheral Rab27B secretory vesicle distribution are poorly understood. Mass spectometry analysis on secretory green fluorescent protein (GFP)-Rab27B vesicles prepared from GFP-Rab27B transfected MCF-7 human breast cancer cells detected eight subunits of the vacuolar H(+)-ATPase (V-ATPase) and presence of V(0) a1 and V(0) d1 subunits was confirmed by Western blot analysis. Reversible inhibition of V-ATPase activity by bafilomycin A1 or transient silencing of V(0) a1 or V(0) d1 subunits demonstrated that V-ATPase controls peripheral localization and size of Rab27B vesicles. V-ATPase expression and activity further controls Rab27B-induced collagen type I invasion, cell cycle progression and invasive growth in the chorioallantoic membrane (CAM) assay. In agreement, Rab27B-dependent extracellular heat-shock protein (HSP)90α release and matrix metalloprotease (MMP)-2 activation is markedly reduced by bafilomycin A1 and transient silencing of V(0) a1 and V(0) d1 subunits. Poor prognosis ERα-positive primary breast tumors expressing high levels of Rab27B also expressed multiple V-ATPase subunits and showed a strong cytoplasmic and peripheral V-ATPase V(1) E expression. In conclusion, inhibiting V-ATPase activity by interfering agents and drugs might be an effective strategy for blocking Rab27B-dependent pro-invasive secretory vesicle trafficking in ERα-positive breast cancer patients. © 2013 Wiley Periodicals, Inc.
An Hendrix; Raija Sormunen; Wendy Westbroek; Kathleen Lambein; Hannelore Denys; Gwen Sys; Geert Braems; Rudy Van den Broecke; Veronique Cocquyt; Christian Gespach; Marc Bracke; Olivier De Wever
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-7
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2009 UICC.
Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent, Belgium; Department of Medical Oncology, Ghent, Belgium.
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