Abstract
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.
Original language | English |
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Pages (from-to) | 2264-2274 |
Number of pages | 11 |
Journal | Oncogene |
Volume | 30 |
Issue number | 19 |
DOIs | |
State | Published - 12 May 2011 |
Bibliographical note
Funding Information:This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs (A090030), NRF of Korea Grant funded by the Korean Government (2009-0064401), Mid-career Research Program through NRF grant funded by the MEST (R01-2007-000-20263-0), Seoul R&BD Program (ST090801) and the NCRC program of MOST/KOSEF (R15-2006-020).
Keywords
- Na,K-ATPase
- Src
- TCTP
- tumorigenesis