Egr-1 Mediates Extracellular Matrix-driven Transcription of Membrane Type 1 Matrix Metalloproteinase in Endothelium

Migratory cells translocate membrane type-1 matrix metalloproteinase (MT1-MMP) to podosomes or invadosomes to break extracellular matrix barriers. In this issue, El Azzouzi et al. (2016. J. Cell. Biol. http://dx.doi.org/10.1083/jcb.201510043) describe an unexpected function for the MT1-MMP cytoplasmic domain in imprinting spatial memory for podosome reformation via assembly in membrane islets.

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TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia

Communications Biology ◽

10.1038/s42003-021-02583-3 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Maren Hülsemann ◽

Colline Sanchez ◽

Polina V. Verkhusha ◽

Vera Des Marais ◽

Serena P. H. Mao ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Matrix Metalloproteinase ◽

Cancer Invasion ◽

Matrix Degradation ◽

Invasion And Metastasis ◽

Extracellular Matrix Degradation ◽

Breast Cancer Invasion ◽

Membrane Type

AbstractDuring breast cancer metastasis, cancer cell invasion is driven by actin-rich protrusions called invadopodia, which mediate the extracellular matrix degradation required for the success of the invasive cascade. In this study, we demonstrate that TC10, a member of a Cdc42 subfamily of p21 small GTPases, regulates the membrane type 1 matrix metalloproteinase (MT1-MMP)-driven extracellular matrix degradation at invadopodia. We show that TC10 is required for the plasma membrane surface exposure of MT1-MMP at these structures. By utilizing our Förster resonance energy transfer (FRET) biosensor, we demonstrate the p190RhoGAP-dependent regulation of spatiotemporal TC10 activity at invadopodia. We identified a pathway that regulates invadopodia-associated TC10 activity and function through the activation of p190RhoGAP and the downstream interacting effector Exo70. Our findings reveal the role of a previously unknown regulator of vesicular fusion at invadopodia, TC10 GTPase, in breast cancer invasion and metastasis.

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TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia

10.1101/2020.11.17.386854 ◽

2020 ◽

Author(s):

M. Hülsemann ◽

S.K. Donnelly ◽

P.V. Verkhusha ◽

S.P.H. Mao ◽

J.E. Segall ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Matrix Metalloproteinase ◽

Cancer Metastasis ◽

Small Gtpases ◽

Matrix Degradation ◽

Invasion And Metastasis ◽

Extracellular Matrix Degradation ◽

Membrane Type

AbstractDuring breast cancer metastasis, cancer cell invasion is driven by actin-rich protrusions called invadopodia, which mediate the extracellular matrix degradation required for the success of the invasive cascade. In this study, we demonstrated that TC10, a member of a Cdc42 subfamily of p21 small GTPases, regulates the membrane type 1 matrix metalloproteinase (MT1-MMP)-driven extracellular matrix degradation at invadopodia. We show that TC10 is required for the plasma membrane surface exposure of MT1-MMP at invadopodia. By utilizing our new Förster resonance energy transfer (FRET) biosensor, we demonstrated the p190RhoGAP-dependent regulation of spatiotemporal TC10 activity at invadopodia. We identified a pathway that regulates TC10 activity and function at invadopodia through the activation of p190RhoGAP and the downstream interacting effector Exo70 at the invadopodia sites. Our findings reveal the role of a previously unknown regulator of vesicular fusion at invadopodia, TC10, on the invasive potential of breast cancer cells during invasion and metastasis.

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Faculty Opinions recommendation of Extracellular matrix-mediated membrane-type 1 matrix metalloproteinase expression in pancreatic ductal cells is regulated by transforming growth factor-beta1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1013507.387931 ◽

2006 ◽

Author(s):

M Sharon Stack

Keyword(s):

Extracellular Matrix ◽

Growth Factor ◽

Matrix Metalloproteinase ◽

Transforming Growth Factor ◽

Transforming Growth Factor Beta1 ◽

Ductal Cells ◽

Pancreatic Ductal Cells ◽

Membrane Type

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EMMPRIN (CD 147) is a central activator of extracellular matrix degradation by Chlamydia pneumoniae-infected monocytes.

Thrombosis and Haemostasis ◽

10.1160/th05-07-0465 ◽

2006 ◽

Vol 95 (01) ◽

pp. 151-158 ◽

Cited By ~ 22

Author(s):

Roland Schmidt ◽

Vanessa Redecke ◽

Yoshi Breitfeld ◽

Nina Wantia ◽

Thomas Miethke ◽

...

Keyword(s):

Extracellular Matrix ◽

Matrix Metalloproteinase ◽

Chlamydia Pneumoniae ◽

Surface Expression ◽

Heat Shock Protein 60 ◽

Membrane Type ◽

Activation Pathways ◽

Accelerate Atherosclerosis

Summary Chlamydia (C.) pneumoniae are thought to infect monocytes and use them as vectors into the vessel wall, where they may accelerate atherosclerosis. We investigated the effects of C. pneumoniae on monocytic matrix metalloproteinase (MMP) activation with focus on the role of the extracellular matrix metalloproteinase inducer EMMPRIN. Human monocytes or monocytic MonoMac6 cells were infected with C. pneumoniae. Infection enhanced mRNA-and surface expression of EMMPRIN and Membrane-type-1 Matrix Metalloproteinase (MT1-MMP), plus the secretion of MMP-7, MMP-9 and the urokinase receptor (uPAR). Chlamydial heat shock protein 60 was identified to be partially responsible for EMMPRIN and MMP-9 induction, while C. trachomatis-infection had no stimulatory effect, indicatinga C. pneumoniae-specific activation pathway. Suppression of EMMPRIN by gene silencing almost completely hindered the induction of MT1-MMP and MMP-9 by C. pneumoniae, suggesting a predominant regulatory role for EMMPRIN. Moreover, C. pneumoniae-infected monocytes exhibited increased MMP-and plasmin-dependent migration through “matrigel”. Additionally, incubation of SMCs with supernatants of C. pneumoniae-infected monocytes induced MMP-2 activation, which was inhibited by IL1-Receptor antagonist or anti-IL-6-mAb, indicating paracrine intercellular activation pathways. In conclusion,C. pneumoniae induce MMP activity directly in monocytes through an EMMPRINdependent pathway and indirectly in SMCs via monocytederived cytokines.

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