Interleukin-24 inhibits osteosarcoma cell migration and invasion via the JNK/c-Jun signaling pathways

Baobiao Zhuo1, Yingchun Shi1, Haihui Qin1

  • 1Department of Surgery, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221006, P.R. China.

Oncology Letters
|June 11, 2017
PubMed

Insights

Interleukin-24 (IL-24) effectively suppresses osteosarcoma metastasis by inhibiting cell migration and invasion. This finding suggests IL-24

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metastatic osteosarcoma has a poor prognosis with current treatments.
  • Effective treatments for osteosarcoma metastasis are urgently needed.
  • Interleukin-24 (IL-24) has shown potential in inhibiting cancer cell growth.

Purpose of the Study:

  • To investigate the potential of IL-24 as a therapeutic agent against osteosarcoma metastasis.
  • To determine the mechanism by which IL-24 affects osteosarcoma cell invasion and migration.

Main Methods:

  • Utilized spontaneously metastasizing human 143B osteosarcoma cells.
  • Assessed the effect of IL-24 on cell migration and invasion.
  • Investigated the involvement of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway.
  • Measured the expression of matrix metalloproteinase (MMP)-2 and MMP-9.

Main Results:

  • IL-24 significantly inhibited migration and invasion in 143B osteosarcoma cells.
  • IL-24 suppressed the phosphorylation of JNK and c-Jun.
  • Downregulation of MMP-2 and MMP-9 expression was observed following IL-24 treatment.
  • These molecular changes contributed to the suppression of cell migration and invasion.

Conclusions:

  • IL-24 demonstrates potent metastasis-suppressive activity in highly metastatic osteosarcoma cells.
  • IL-24 acts via the JNK/c-Jun signaling pathway to reduce MMP-2 and MMP-9 levels.
  • IL-24 holds translational potential as a therapeutic agent for metastatic osteosarcoma.

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.4K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.4K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.4K