Silencing of galectin-3 represses osteosarcoma cell migration and invasion through inhibition of FAK/Src/Lyn activation and β-catenin expression and increases susceptibility to chemotherapeutic agents

Int J Oncol. 2015 Jan;46(1):185-94. doi: 10.3892/ijo.2014.2721. Epub 2014 Oct 22.

Abstract

Galectin-3 is involved in tumor cell proliferation, adhesion, angiogenesis and metastasis. Galectin-3 promotes β-catenin/Wnt signaling, and β-catenin-related oncogenesis has been frequently reported in osteosarcoma. However, the correlation between galectin-3 and β‑catenin signaling in osteosarcoma is poorly defined. We hypothesized that galectin-3 may control the migration and invasion of cancer cells and that silencing of galectin-3 would therefore, suppress motility in osteosarcoma cells. In the present study, we show that galectin-3 silencing in cultured human osteosarcoma cells had decreased cell migration and invasion capabilities; reduced the expression and activation of FAK, Src, Lyn, PI3K/Akt, ERK1/2 and β-catenin, which are key mediators of invasion; inhibited the expression and secretion of VEGF, MCP-1, IL-8, IL-6, MMP2/9 and phospho-Stat3; and potentiated sensitivity to cisplatin. Our results suggest that galectin-3 may be a feasible therapeutic target for osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Cell Movement* / drug effects
  • Cell Movement* / genetics
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Galectin 3 / antagonists & inhibitors
  • Galectin 3 / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Silencing*
  • Humans
  • Neoplasm Invasiveness
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Tumor Cells, Cultured
  • beta Catenin / genetics*
  • beta Catenin / metabolism
  • src-Family Kinases / metabolism

Substances

  • Antineoplastic Agents
  • CTNNB1 protein, human
  • Galectin 3
  • beta Catenin
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • lyn protein-tyrosine kinase
  • src-Family Kinases