title: Supporting a role for the GTPase Rab7 in prostate cancer progression.
abstract: 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.
authors: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Department of Natural Science, Dickinson State University, Dickinson, North Dakota, United States of America.
authors: Joshua J
authors: JJ
authors: Steffan
authors: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: Samantha S
authors: SS
authors: Dykes
authors: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: David T
authors: DT
authors: Coleman
authors: Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: Lisa K
authors: LK
authors: Adams
authors: Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: Donna
authors: D
authors: Rogers
authors: Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: Jennifer L
authors: JL
authors: Carroll
authors: Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Department of Urology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: B Jill
authors: BJ
authors: Williams
authors: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America ; Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
authors: James A
authors: JA
authors: Cardelli
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D045162:Thiazolidinediones; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D025521:Tumor Suppressor Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; C089946:2,4-thiazolidinedione; D020691:rab GTP-Binding Proteins