Bae Seong-Yeon, Kim Hyun Jung, Lee Kong-Joo, Lee Kyunglim
Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Sci Rep. 2015 Jan 27;5:8061. doi: 10.1038/srep08061.
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.
翻译调控肿瘤蛋白（TCTP）是一种高度保守的蛋白质，参与细胞增殖与生长、肿瘤发生、细胞凋亡、多能性以及细胞周期调控等基本过程。TCTP还能抑制钠钾ATP酶，其亚基被认为是上皮-间质转化（EMT）的标志物，而EMT是肿瘤侵袭、转移和纤维化过程中的关键步骤。我们推测，TCTP可能也是一种EMT诱导剂。本研究旨在验证这一假设。我们发现，在猪肾近端小管细胞系LLC-PK1中过表达TCTP会诱导出类似EMT的表型，并伴有预期的形态学变化以及EMT相关标志物的出现。相反，敲低TCTP可逆转这些EMT表型的诱导。TCTP过表达还通过激活mTORC2/Akt/GSK3β/β-连环蛋白增强细胞迁移，并通过激活MMP-9增强细胞侵袭能力。此外，黑色素瘤细胞中TCTP的敲低通过抑制间充质样表型的发展显著减少了肺转移。总体而言，这些发现支持了我们的假设，即TCTP是EMT的正向调节因子，并表明调节TCTP表达是一种抑制癌细胞侵袭和迁移以及包括转移在内的相关病理过程的潜在方法。
