Translationally controlled tumor protein induces epithelial to mesenchymal transition and promotes cell migration, invasion and metastasis

Seong Yeon Bae, Hyun Jung Kim, Kong Joo Lee, Kyunglim Lee

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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.

Original languageEnglish
Article number8061
Pages (from-to)8061
Number of pages1
JournalScientific Reports
StatePublished - Jan 2015

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health Technology R&D Project, Ministry of Health & Welfare [A111417(HI11C1371)] and National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning (MSIP) [2012R1A1A2042142] [2012M3A9A8053272] to K. Lee, NRF Grant funded by the Korean Government (NRF-2011-Global Ph.D. Fellowship Program) to S. Y. Bae and RP-Grant 2013 of Ewha Womans University to H. J. Kim.


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