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Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src
- Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src
- Jung J.; Kim H.Y.; Kim M.; Sohn K.; Lee K.
- Ewha Authors
- SCOPUS Author ID
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- vol. 30, no. 19, pp. 2264 - 2274
- SCI; SCIE; SCOPUS
- Translationally controlled tumor protein (TCTP) is implicated in cell growth and malignant transformation. TCTP has been found to interact directly with the third cytoplasmic domain of the α subunit of Na,K-ATPase, but whether this interaction has a role in tumorigenesis is unclear. In this study, we examined TCTP-induced tumor progression signaling networks in human breast epithelial cells, using adenoviral infection. We found that TCTP (a) induces Src release from Na,K-ATPase α subunit and Src activation; (b) phosphorylates tyrosine residues 845, 992, 1086, 1148 and 1173 on anti-epidermal growth factor receptor (EGFR); (c) activates PI3K (phosphatidylinositol 3-kinase)-AKT, Ras-Raf-MEK-ERK1/2, Rac-PAK1/2, MKK3/6-p38 and phospholipase C (PLC)-γ pathways; (d) enhances NADPH oxidase-dependent reactive oxygen species (ROS) generation; (e) stimulates cytoskeletal remodeling and cell motility and (f) upregulates matrix metalloproteinase (MMP) 3 and 13. These findings suggest that TCTP induces tumorigenesis through distinct multicellular signaling pathways involving Src-dependent EGFR transactivation, ROS generation and MMP expression. © 2011 Macmillan Publishers Limited All rights reserved.
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