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Updated: Jun 20, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
ECRG2 regulates cell migration/invasion through urokinase-type plasmin activator receptor (uPAR)/beta1 integrin
Xiaolong Cheng1, Zheng Shen, Litian Yin
1Department of Anatomy, Shanxi Medical University, Taiyuan, Shanxi 030001, China.
Abstract:
ECRG2 is a novel gene that shows sequence similarity to KAZAL-type serine protease inhibitor. We have previously demonstrated that ECRG2 inhibits migration/invasion of lung cancer PG cells. However, the mechanism by which ECRG2 performs these activities is a compelling question. Urokinase-type plasmin activator (uPA) binding to uPAR induces migration/invasion through multiple interactors including integrins. In this study, we found that ECRG2 binds specifically to the kringle domain of uPA. Moreover, we demonstrated that ECRG2 forms a complex with uPA.uPAR, that such a complex modifies the dynamical association of uPAR with beta1 integrins, and that disruption inhibits Src/MAP (mitogen-activated protein) kinase pathway, resulting in suppression of cell migration/invasion in an in vitro Matrigel migration/invasion assay. Conversely, depletion of ECRG2 markedly enhanced the association of uPAR with beta1 integrins, elevated basal Src/MAP kinase activation, and stimulated HT1080, MDA-MB-231, and MCF-7 cell migration/invasion. Together, our results provide evidence that ECRG2 is involved in the regulation of migration/invasion through uPA/uPAR/beta1 integrins/Src/MAP kinase pathway and may represent a novel therapeutic target for cancer.
Insights
ECRG2 protein inhibits cancer cell migration by disrupting the uPA/uPAR/integrin pathway, impacting Src/MAP kinase signaling. This finding reveals ECRG2 as a potential therapeutic target for reducing cancer invasion.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- ECRG2 (Endometrial Carcinoma Related Gene 2) is a KAZAL-type serine protease inhibitor.
- Previous studies showed ECRG2 inhibits lung cancer cell migration and invasion.
- The precise mechanism of ECRG2's action remained unclear.
Purpose of the Study:
- To elucidate the molecular mechanism by which ECRG2 suppresses cancer cell migration and invasion.
- To investigate the interaction of ECRG2 with the urokinase-type plasmin activator (uPA) system.
Main Methods:
- Investigated ECRG2 binding to uPA.
- Analyzed the formation of ECRG2-uPA-uPAR complexes.
- Assessed the impact of these complexes on beta1 integrin association and Src/MAP kinase pathway activation.
- Utilized in vitro Matrigel migration/invasion assays.
- Examined cell migration in response to ECRG2 depletion in various cancer cell lines (HT1080, MDA-MB-231, MCF-7).
Main Results:
- ECRG2 specifically binds to the kringle domain of uPA.
- ECRG2 forms a complex with uPA and uPAR, altering uPAR dynamics with beta1 integrins.
- This complex formation inhibits the Src/MAP kinase pathway, suppressing cell migration and invasion.
- Depletion of ECRG2 enhanced uPAR-beta1 integrin association, increased Src/MAP kinase activation, and promoted cell migration/invasion.
Conclusions:
- ECRG2 regulates cancer cell migration and invasion by modulating the uPA/uPAR/beta1 integrins/Src/MAP kinase pathway.
- ECRG2's mechanism involves disrupting key signaling complexes essential for cell motility.
- ECRG2 represents a promising novel therapeutic target for inhibiting cancer metastasis.
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