Membrane type 1-matrix metalloproteinase: Substrate diversity in pericellular proteolysis☆

Barbolina, Maria V.; Stack, M. Sharon

doi:10.1016/j.semcdb.2007.06.008

Cited by 129 publications

(139 citation statements)

References 108 publications

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“…MT1-MMP directly degrades components of the ECM, thus, providing a highly regulated mechanism through which protein cleavage is localized to sites of cell-matrix contact during the process of metastasis (3,5,41). Importantly, genetic studies support the role of MT1-MMP as a primary FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

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Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Dangi-Garimella

Redig

Shields

et al. 2010

Journal of Biological Chemistry

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Matrix metalloproteinases (MMPs) 2 are a large family of highly conserved metalloendopeptidases with proteolytic activity directed against a variety of extracellular matrix (ECM) substrates (1-3). MMPs have been implicated in basement membrane proteolysis, activation of growth factors, and cleavage of cell-adhesion molecules. Extending mechanistic investigation to cancer biology, numerous studies have shown that MMP overexpression enhances the invasive activity of tumor cell lines (4 -6). Analysis of human disease further supports the pro-tumorigenic role of MMPs, as increased expression of these proteases in tumor samples is clinically associated with invasion, metastasis, poor prognosis, and shorter survival times (7,8). In the specific case of squamous cell carcinoma (SCC), increased expression of membrane type 1-MMP (MT1-MMP, MMP14) is associated with ECM breakdown, tissue invasion, and lymph node metastasis (8).However, several animal studies have now clearly demonstrated that multiple members of the MMP family provide a paradoxically protective effect during the relentless molecular destruction that characterizes malignant progression. MMPs may have been initially identified as potent pro-tumorigenic proteases, but their simultaneous ability to function in an opposing, anti-tumorigenic role is now equally well established (9, 10). Such data underscore both the complexity of MMP activity in cellular signaling events as well as the importance of stringently evaluating the context in which these proteases take on either an anti-tumorigenic or pro-tumorigenic role. Intriguingly, several recent studies using SCC models have begun to suggest a putative mechanism through which MMPs may be induced to function primarily as anti-tumorigenic proteases. When exposed to carcinogens, MMP3-null mice developed squamous cell skin cancers that not only grew faster but were also strikingly less differentiated than those of control animals (11). Significantly, orthotopic injection of MMP3-expressing tumor cells resulted in pronounced tumor cell differentiation (12). However, although such findings indicate that MMPs may inhibit SCC progression by promoting tumor cell differentiation, the precise mechanism through which these proteinases regulate this process has not yet been elucidated.In normal tissue keratinocyte differentiation is a complex process mediated by cell-ECM and cell-cell interactions that subsequently activate downstream signaling pathways (13-15). Specifically, among structural proteins, integrins mediate primarily cell-ECM interactions, whereas cadherins are responsible for cell-cell interactions (13). In vitro activation of integrins or inhibition of cadherins after ligation or dominant negative expression, respectively, results in negative regulation of human keratinocyte differentiation (16 -18). Furthermore, beyond structural proteins, Rho GTPases are also known to be an important component of keratinocyte differentiation pathways. Rho signaling has been shown to mediate cell-cell and cell-matrix adhesion...

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Section: Discussionmentioning

confidence: 99%

“…Matrix metalloproteinases (MMPs) 2 are a large family of highly conserved metalloendopeptidases with proteolytic activity directed against a variety of extracellular matrix (ECM) substrates (1)(2)(3). MMPs have been implicated in basement membrane proteolysis, activation of growth factors, and cleavage of cell-adhesion molecules.…”

mentioning

confidence: 99%

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Dangi-Garimella

Redig

Shields

et al. 2010

Journal of Biological Chemistry

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“…There are 23 different human MMPs described to date, some of which are secreted in the pericellular environment while others are associated with the cell membrane. Membrane type-1 MMP (MT1-MMP, , the best characterized membrane-anchored MMP, is a potent matrix-degrading proteinase that digests a broad spectrum of ECM proteins, including COL1 (Ohuchi et al, 1997), as well as a number of cell surface-associated proteins (Barbolina and Stack, 2008). In addition to its catalytic domain, MMP-14 contains a short cytoplasmic sequence that is involved in the regulation of the enzyme activity and in the activation of signal transduction processes (Gingras and Be´liveau, 2010).…”

Section: Introductionmentioning

confidence: 99%

MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis

et al. 2011

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As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this novel microenvironment. Collagen influences the fate of epithelial cells by inducing apoptosis. However, the mechanisms used by invading tumor cells to evade collagen-induced apoptosis remain to be defined. We demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14) confers breast cancer cells with the ability to escape apoptosis when embedded in a collagen gel and after orthotopic implantation in vivo. In the absence of MMP-14-dependent proteolysis, type I collagen triggers apoptosis by inducing the expression of the pro-apoptotic Bcl-2-interacting killer in luminallike breast cancer cells. These findings reveal a new mechanism whereby MMP-14 activity promotes tumor progression by circumventing apoptosis.

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“…There is a consensus among researchers that pro-invasive MT1-MMP is a key element in tumor cell migration and pericellular proteolysis (7)(8)(9)(10)(11). To become catalytically active, the latent MT1-MMP proenzyme requires proteolytic removal of its inhibitory prodomain (12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

Non-destructive and Selective Imaging of the Functionally Active, Pro-invasive Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Enzyme in Cancer Cells

Remacle

Shiryaev

Golubkov

et al. 2013

Journal of Biological Chemistry

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Background: MT1-matrix metalloproteinase (MMP) is directly related to cell migration, invasion, and metastasis. Results: We developed a fluorescent reporter that targets the active cellular MT1-MMP enzyme alone. Conclusion: The reporter quantifies the active MT1-MMP enzyme levels in multiple cell types. Significance: The reporter will contribute to the design of novel, more efficient prognostic approaches and personalized cancer therapies.

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Membrane type 1-matrix metalloproteinase: Substrate diversity in pericellular proteolysis☆

Cited by 129 publications

References 108 publications

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

Rho-ROCK-Myosin Signaling Meditates Membrane Type 1 Matrix Metalloproteinase-induced Cellular Aggregation of Keratinocytes

MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis

Non-destructive and Selective Imaging of the Functionally Active, Pro-invasive Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Enzyme in Cancer Cells

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