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Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis

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...

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Autores principales: Bae, Seong-Yeon, Kim, Hyun Jung, Lee, Kong-Joo, Lee, Kyunglim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306963/
https://www.ncbi.nlm.nih.gov/pubmed/25622969
http://dx.doi.org/10.1038/srep08061
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author Bae, Seong-Yeon
Kim, Hyun Jung
Lee, Kong-Joo
Lee, Kyunglim
author_facet Bae, Seong-Yeon
Kim, Hyun Jung
Lee, Kong-Joo
Lee, Kyunglim
author_sort Bae, Seong-Yeon
collection PubMed
description 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.
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spelling pubmed-43069632015-02-06 Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis Bae, Seong-Yeon Kim, Hyun Jung Lee, Kong-Joo Lee, Kyunglim Sci Rep Article 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. Nature Publishing Group 2015-01-27 /pmc/articles/PMC4306963/ /pubmed/25622969 http://dx.doi.org/10.1038/srep08061 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Bae, Seong-Yeon
Kim, Hyun Jung
Lee, Kong-Joo
Lee, Kyunglim
Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
title Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
title_full Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
title_fullStr Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
title_full_unstemmed Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
title_short Translationally Controlled Tumor Protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
title_sort translationally controlled tumor protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306963/
https://www.ncbi.nlm.nih.gov/pubmed/25622969
http://dx.doi.org/10.1038/srep08061
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