title: Oncogenic role of rab escort protein 1 through EGFR and STAT3 pathway.
abstract: Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts. REP1 expression was also elevated in A549 lung cancer cells and HT-29 colon cancer cells compared with BEAS-2B normal lung and CCD-18Co normal colon epithelial cells, respectively. Interestingly, short interfering RNA (siRNA)-mediated REP1 knockdown-induced growth inhibition of cancer cell lines via downregulation of EGFR and inactivation of STAT3, but had a negligible effect on normal cell lines. Moreover, overexpression of REP1 in BEAS-2B cells enhanced cell growth and anchorage-independent colony formation with little increase in EGFR level and STAT3 activation. Furthermore, REP1 knockdown effectively reduced tumor growth in a mouse xenograft model via EGFR downregulation and STAT3 inactivation in vivo. These data suggest that REP1 plays an oncogenic role, driving tumorigenicity via EGFR and STAT3 signaling, and is a potential therapeutic target to control cancers.
authors.affiliation: Comparative Biomedicine Research Branch, Division of Cancer Biology, National Cancer Center, Goyang, Korea.
authors.forename: Un-Jung
authors.initials: UJ
authors.lastname: Yun
authors.affiliation: Pediatric Oncology Branch, National Cancer Center, Goyang, Korea.
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Sung
authors.affiliation: Department of Pathology, National Cancer Center, Goyang, Korea.
authors.forename: Seog-Yun
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Korea.
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.affiliation: Comparative Biomedicine Research Branch, Division of Cancer Biology, National Cancer Center, Goyang, Korea.
authors.forename: Jaegal
authors.initials: J
authors.lastname: Shim
authors.affiliation: Department of Molecular Medicine, College of Medicine, Inha University, Incheon, Korea.
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Bioscience and Biotechnology Center, Nagoya University, Nagoya, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hibi
authors.affiliation: Comparative Biomedicine Research Branch, Division of Cancer Biology, National Cancer Center, Goyang, Korea.
authors.forename: Young-Ki
authors.identifier: 0000-0001-7964-3540
authors.initials: YK
authors.lastname: Bae
authors.affiliation: Comparative Biomedicine Research Branch, Division of Cancer Biology, National Cancer Center, Goyang, Korea.
authors.forename: Yong-Nyun
authors.initials: YN
authors.lastname: Kim
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015794:Choroideremia / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors