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

J Jung1, H Y Kim, M Kim

  • 1College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.

Oncogene
|February 1, 2011
PubMed

Insights

Translationally controlled tumor protein (TCTP) promotes tumor growth by activating signaling pathways. TCTP induces Src activation, EGFR transactivation, and matrix metalloproteinase expression, driving cell motility and progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Translationally controlled tumor protein (TCTP) is linked to cell growth and cancer.
  • TCTP's interaction with Na,K-ATPase α subunit suggests a role in tumorigenesis, but this is not well understood.

Purpose of the Study:

  • To investigate the signaling networks initiated by TCTP in human breast epithelial cells.
  • To elucidate the mechanisms by which TCTP contributes to tumor progression.

Main Methods:

  • Adenoviral infection was used to introduce TCTP into human breast epithelial cells.
  • Analysis of signaling pathway activation, protein phosphorylation, reactive oxygen species generation, and matrix metalloproteinase expression.

Main Results:

  • TCTP induced Src release and activation, and subsequent epidermal growth factor receptor (EGFR) transactivation.
  • Activation of multiple signaling pathways including PI3K-AKT, Ras-Raf-MEK-ERK1/2, and Rac-PAK1/2.
  • Enhanced reactive oxygen species (ROS) generation, cytoskeletal remodeling, cell motility, and upregulation of matrix metalloproteinases (MMPs) 3 and 13.

Conclusions:

  • TCTP promotes tumorigenesis via Src-dependent EGFR transactivation, ROS generation, and MMP expression.
  • These findings reveal TCTP's role in distinct multicellular signaling pathways crucial for cancer progression.

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