Open AccessSupporting a Role for the GTPase Rab7 in Prostate Cancer Progression
Author(s) -
Joshua J. Steffan,
Samantha S. Dykes,
David T. Coleman,
Lisa K. Adams,
Donna Rogers,
Jennifer L. Carroll,
B. Jill Williams,
James A. Cardelli
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0087882
Subject(s) - rab , cancer research , prostate cancer , microbiology and biotechnology , biology , gtpase , lysosome , mediator , metastasis , signal transduction , dishevelled , cancer , wnt signaling pathway , biochemistry , frizzled , genetics , enzyme
Invasion and subsequent metastasis is the major cause of death from most cancers including prostate cancer. Herein we report on the potential tumor suppressive properties of Rab7, a GTPase that regulates trafficking of lysosomes. The movement of lysosomes to the cell surface in response to environmental cues increases the secretion of proteinases and cell invasion. We determined that Troglitazone and other members of the Thiazolidinedione family inhibit cell-surface directed lysosome trafficking and cathepsin B secretion through a Rab7-dependent mechanism. Moreover, Rab7 shRNA expressing cells were found to be more invasive in vitro and in vivo . Increased invasiveness was accompanied by elevated expression of the c-Met receptor and prolonged downstream signaling, thereby supporting a role for Rab7 as a mediator of signaling down-regulation. Taken together, these results suggested that Rab7 acts as a negative regulator of prostate tumor growth and invasion, providing further evidence for its potential as a tumor suppressor.