Related Experiment Video
Updated: Jun 18, 2026

Real-time Imaging of Leukotriene B4 Mediated Cell Migration and BLT1 Interactions with β-arrestin
Published on: December 23, 2010
Ras-induced invasion and metastasis are regulated by a leukotriene B4 receptor BLT2-linked pathway
1Inflammatory Signaling Laboratory, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Abstract:
Ras signaling pathways are well-recognized for their involvement in cancer cell proliferation; however, considerably less is known regarding their contribution to invasion and metastasis. Here, we demonstrate that a novel BLT2, a low-affinity leukotriene B(4) receptor-linked signaling cascade involving the generation of reactive oxygen species (ROS) via Nox1, NF-kappaB stimulation and subsequent upregulation of matrix metalloproteinase-9 (MMP-9) is a potential mechanism by which Ras promotes invasion and metastasis. We found that inhibition of BLT2 signaling markedly suppressed Ras-evoked metastasis and reduced the associated mortality in mice. Consistent with the proposed role of BLT2 as a key downstream mediator of Ras signaling to metastasis, BLT2 expression alone resulted in the formation of numerous metastatic lung nodules and the nodules formation was significantly attenuated by the inhibition of MMP-9, a downstream component of BLT2. Together, our results reveal the previously unsuspected function of BLT2-linked cascade in driving oncogenic Ras-induced metastasis and would provide a valuable insight into invasion and metastasis.
Insights
Oncogenic Ras promotes cancer metastasis through a novel signaling pathway involving the BLT2 receptor, reactive oxygen species (ROS), and MMP-9. Inhibiting this pathway suppressed metastasis and reduced mortality in mice.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Ras signaling pathways are crucial for cancer cell proliferation.
- Their role in cancer invasion and metastasis is less understood.
- Identifying novel pathways is key to understanding cancer progression.
Purpose of the Study:
- To investigate the role of BLT2 signaling in Ras-driven cancer metastasis.
- To elucidate the mechanism linking Ras to invasion and metastasis.
- To identify potential therapeutic targets for metastatic cancers.
Main Methods:
- Investigated a BLT2-linked signaling cascade involving ROS generation via Nox1.
- Examined NF-kappaB stimulation and matrix metalloproteinase-9 (MMP-9) upregulation.
- Assessed the effect of BLT2 inhibition on Ras-evoked metastasis in mouse models.
- Evaluated the impact of MMP-9 inhibition on BLT2-induced metastasis.
Main Results:
- A novel BLT2 signaling cascade (ROS, Nox1, NF-kappaB, MMP-9) was identified as a mechanism for Ras-driven invasion and metastasis.
- Inhibition of BLT2 signaling significantly suppressed Ras-evoked metastasis and reduced mortality in mice.
- BLT2 expression alone induced metastatic lung nodules, which were attenuated by MMP-9 inhibition.
Conclusions:
- The BLT2-linked cascade is a previously unrecognized driver of oncogenic Ras-induced metastasis.
- BLT2 acts as a key downstream mediator of Ras signaling in metastasis.
- Targeting the BLT2 pathway offers a potential strategy to combat cancer invasion and metastasis.
Related Concept Videos
Regulation of Angiogenesis and Blood Supply
Interactions Between Signaling Pathways
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...
Acute Inflammation II: Cellular Phase
MAPK Signaling Cascades
Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...

