scholarly journals Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis

2009 ◽  
Vol 20 (7) ◽  
pp. 2030-2040 ◽  
Author(s):  
Marc A. Lafleur ◽  
Daosong Xu ◽  
Martin E. Hemler
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Invasion ◽  
Three Dimensional ◽  
Tumor Cell Invasion ◽  
Collagen Gels ◽  
Invasion And Metastasis ◽  
Lysosomal Degradation ◽  
Membrane Type ◽  
Pericellular Proteolysis

Membrane type-1 matrix metalloproteinase (MT1-MMP) supports tumor cell invasion through extracellular matrix barriers containing fibrin, collagen, fibronectin, and other proteins. Here, we show that simultaneous knockdown of two or three members of the tetraspanin family (CD9, CD81, and TSPAN12) markedly decreases MT1-MMP proteolytic functions in cancer cells. Affected functions include fibronectin proteolysis, invasion and growth in three-dimensional fibrin and collagen gels, and MMP-2 activation. Tetraspanin proteins (CD9, CD81, and TSPAN2) selectively coimmunoprecipitate and colocalize with MT1-MMP. Although tetraspanins do not affect the initial biosynthesis of MT1-MMP, they do protect the newly synthesized protein from lysosomal degradation and support its delivery to the cell surface. Interfering with MT1-MMP-tetraspanin collaboration may be a useful therapeutic approach to limit cancer cell invasion and metastasis.

Neutrophil-derived serine proteinases enhance membrane type-1 matrix metalloproteinase–dependent tumor cell invasion

Surgery ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Peter Shamamian ◽  
Ben J.Z. Pocock ◽  
Jess D. Schwartz ◽  
Sara Monea ◽  
Neal Chuang ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Serine Proteinases ◽  
Membrane Type

scholarly journals Microenvironmental Regulation of Membrane Type 1 Matrix Metalloproteinase Activity in Ovarian Carcinoma Cells via Collagen-induced EGR1 Expression

2006 ◽  
Vol 282 (7) ◽  
pp. 4924-4931 ◽  
Author(s):  
Maria V. Barbolina ◽  
Brian P. Adley ◽  
Edgardo V. Ariztia ◽  
Yueying Liu ◽  
M. Sharon Stack
Keyword(s):  
Matrix Metalloproteinase ◽  
Ovarian Carcinoma ◽  
Three Dimensional ◽  
Carcinoma Cells ◽  
Collagenolytic Activity ◽  
Type I ◽  
Collagen Gels ◽  
Ovarian Carcinoma Cells ◽  
Membrane Type

Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, and collagen-induced integrin clustering up-regulates the expression of the transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity is important in intraperitoneal metastasis, potentiating invasion through the mesothelial cell layer and colonization of the submesothelial collagen-rich matrix. The objective of this study was to elucidate a potential mechanistic link between collagen adhesion and MT1-MMP expression. Our results indicate that culturing cells on three-dimensional collagen gels, but not thin layer collagen or synthetic threedimensional hydrogels, results in rapid induction of the transcription factor EGR1. Integrin signaling through a SRC kinase-dependent pathway is necessary for EGR1 induction. Silencing of EGR1 expression using small interfering RNA abrogated collagen-induced MT1-MMP expression and inhibited cellular invasion of three-dimensional collagen gels. These data support a model for intraperitoneal metastasis wherein collagen adhesion and clustering of collagen binding integrins activates integrin-mediated signaling via SRC kinases to induce expression of EGR1, resulting in transcriptional activation of the MT1-MMP promoter and subsequent MT1-MMP-catalyzed collagen invasion. This model highlights the role of unique interactions between ovarian carcinoma cells and interstitial collagens in the ovarian tumor microenvironment in inducing gene expression changes that potentiate intraperitoneal metastatic progression.

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

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.

scholarly journals The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression

2002 ◽  
Vol 110 (12) ◽  
pp. 1831-1838 ◽  
Author(s):  
Enrique Lara-Pezzi ◽  
Maria Victoria Gómez-Gaviro ◽  
Beatriz G. Gálvez ◽  
Emilia Mira ◽  
Miguel A. Iñiguez ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Matrix Metalloproteinase ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
X Protein ◽  
Matrix Metalloproteinase 1 ◽  
B Virus ◽  
Membrane Type

scholarly journals Author Correction: TC10 regulates breast cancer invasion and metastasis by controlling membrane type-1 matrix metalloproteinase at invadopodia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Maren Hülsemann ◽  
Colline Sanchez ◽  
Polina V. Verkhusha ◽  
Vera Des Marais ◽  
Serena P. H. Mao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Invasion ◽  
Invasion And Metastasis ◽  
Breast Cancer Invasion ◽  
Membrane Type
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