Translationally controlled tumor protein induces human breast epithelial cell transformation through the activation of Src

J. Jung, H. Y. Kim, M. Kim, K. Sohn, M. Kim, K. Lee

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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 languageEnglish
Pages (from-to)2264-2274
Number of pages11
JournalOncogene
Volume30
Issue number19
DOIs
StatePublished - 12 May 2011

Keywords

  • Na,K-ATPase
  • Src
  • TCTP
  • tumorigenesis

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