title: Translationally controlled tumor protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis.
abstract: Translationally controlled tumor protein (TCTP), is a highly conserved protein involved in fundamental processes, such as cell proliferation and growth, tumorigenesis, apoptosis, pluripotency, and cell cycle regulation. TCTP also inhibits Na,K-ATPase whose subunits have been suggested as a marker of epithelial-to-mesenchymal transition (EMT), a crucial step during tumor invasiveness, metastasis and fibrosis. We hypothesized that, TCTP might also serve as an EMT inducer. This study attempts to verify this hypothesis. We found that overexpression of TCTP in a porcine renal proximal tubule cell line, LLC-PK1, induced EMT-like phenotypes with the expected morphological changes and appearance of EMT related markers. Conversely, depletion of TCTP reversed the induction of these EMT phenotypes. TCTP overexpression also enhanced cell migration via activation of mTORC2/Akt/GSK3β/β-catenin, and invasiveness by activating MMP-9. Moreover, TCTP depletion in melanoma cells significantly reduced pulmonary metastasis by inhibiting the development of mesenchymal-like phenotypes. Overall, these findings support our hypothesis that TCTP is a positive regulator of EMT and suggest that modulation of TCTP expression is a potential approach to inhibit the invasiveness and migration of cancer cells and the attendant pathologic processes including metastasis.
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Seong-Yeon
authors.initials: SY
authors.lastname: Bae
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Kong-Joo
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Kyunglim
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046912:Multiprotein Complexes / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014184:Transplantation, Homologous; D000090324:Tumor Protein, Translationally-Controlled 1; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; D020780:Matrix Metalloproteinase 9