Related Experiment Video
Updated: Oct 24, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGF-β1 facilitates MT1-MMP-mediated proMMP-9 activation and invasion in oral squamous cell carcinoma cells
Hirari Yamahana1, Minoru Terashima2, Risa Takatsuka2
1Graduate School of Technology, Industrial and Social Science, Tokushima University, Tokushima 770-8506, Japan.
Abstract:
Matrix metalloproteinase (MMP)-2 and MMP-9, also known as gelatinases or type IV collagenases, are recognized as major contributors to the proteolytic degradation of extracellular matrix during tumor invasion. Latent MMP-2 (proMMP-2) is activated by membrane type 1 MMP (MT1-MMP) on the cell surface of tumor cells. We previously reported that cell-bound proMMP-9 is activated by the MT1-MMP/MMP-2 axis in HT1080 cells treated with concanavalin A in the presence of exogenous proMMP-2. However, the regulatory mechanism of proMMP-9 activation remains largely unknown. Transforming growth factor (TGF)-β1 is frequently overexpressed in tumor tissues and is associated with tumor aggressiveness and poor prognosis. In this study, we examined the role of TGF-β1 on MT1-MMP-mediated proMMP-9 activation using human oral squamous cell carcinoma cells. TGF-β1 significantly increased the expression of MMP-9. By adding exogenous proMMP-2, TGF-β1-induced proMMP-9 was activated during collagen gel culture, which was suppressed by the inhibition of TGF-β1 signaling or MT1-MMP activity. This MT1-MMP-mediated proMMP-9 activation was needed to facilitate TGF-β1-induced cell invasion into collagen gel. Thus, TGF-β1 may facilitate MT1-MMP-mediated MMP-9 activation and thereby stimulate invasion of tumor cells in collaboration with MT1-MMP and MMP-2.
Insights
Transforming growth factor-beta 1 (TGF-β1) promotes tumor cell invasion by enhancing matrix metalloproteinase-9 (MMP-9) activation. This process involves membrane type 1 MMP (MT1-MMP) and MMP-2, highlighting a key pathway in cancer progression.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are crucial for extracellular matrix degradation during tumor invasion.
- Membrane type 1 MMP (MT1-MMP) activates proMMP-2 on tumor cell surfaces, and a similar axis involving MT1-MMP and MMP-2 activates cell-bound proMMP-9.
- The precise regulatory mechanisms governing proMMP-9 activation, especially in the context of tumor-promoting factors, remain incompletely understood.
Purpose of the Study:
- To investigate the role of transforming growth factor-beta 1 (TGF-β1) in MT1-MMP-mediated proMMP-9 activation.
- To elucidate the contribution of this activation pathway to TGF-β1-induced tumor cell invasion.
Main Methods:
- Utilized human oral squamous cell carcinoma cells.
- Assessed the effect of TGF-β1 on MMP-9 expression and activation.
- Employed collagen gel culture to evaluate cell invasion.
- Investigated the impact of inhibiting TGF-β1 signaling and MT1-MMP activity on proMMP-9 activation and invasion.
Main Results:
- TGF-β1 significantly upregulated MMP-9 expression.
- TGF-β1-induced proMMP-9 activation, dependent on exogenous proMMP-2, was observed in collagen gel cultures.
- Inhibition of TGF-β1 signaling or MT1-MMP activity suppressed proMMP-9 activation.
- MT1-MMP-mediated proMMP-9 activation was essential for TGF-β1-induced cell invasion.
Conclusions:
- TGF-β1 promotes MT1-MMP-mediated activation of MMP-9, requiring MMP-2.
- This pathway is critical for facilitating TGF-β1-induced invasion of oral squamous cell carcinoma cells.
- TGF-β1 collaborates with MT1-MMP and MMP-2 to enhance tumor cell invasion.
Related Concept Videos
01:16TGF - β Signaling Pathway
01:17Intracellular Signaling Affects Focal Adhesions
Some...
02:17The Tumor Microenvironment