Regulation of matrix metalloproteinase expression

Gorman, Jennifer L.; Ispanovic, Eric; Haas, Tara L.

doi:10.1016/j.ddmod.2011.06.001

Cited by 11 publications

(16 citation statements)

References 70 publications

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“…Consistent with this, these apical actin protrusions were absent in Piezo1 KD cells in which the elevated Src activity was also abolished. Our results also demonstrate the regulatory roles of several key pathways of mechanotransduction in the compressive stress-induced cancer cell invasive phenotype including MMPs, FAK/ERK and calcium, which are consistent with that mechanical force stimulates expression of MMPs, as well as growth factors, often utilizes FAK or ERK signaling pathway, which are activated by calcium signaling 78,79,80 . Our study thus provides a comprehensive understanding from disparate systems in the context of compressioninduced breast cancer cell invasion (Figure 7).…”

Section: Invasion Of Cells Through Layers Of Ecm Is a Critical Activisupporting

confidence: 87%

Compressive Stress Enhances Invasive Phenotype of Cancer Cells via Piezo1 Activation

Luo¹,

Ho²,

Tong³

et al. 2019

Preprint

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Uncontrolled growth in solid tumor generates compressive stress that drives cancer cells into invasive phenotypes, but little is known about how such stress affects the invasion and matrix degradation of cancer cells and the underlying mechanisms.Here we show that compressive stress enhanced invasion, matrix degradation, and invadopodia formation of breast cancer cells. We further identified Piezo1 channels as the putative mechanosensitive cellular components that transmit the compression to induce calcium influx, which in turn triggers activation of RhoA, Src, FAK, and ERK signaling, as well as MMP-9 expression. Interestingly, for the first time we observed invadopodia with matrix degradation ability on the apical side of the cells, similar to those commonly observed at the cell's ventral side. Furthermore, we demonstrate that Piezo1 and caveolae were both involved in mediating the compressive stress-induced cancer cell invasive phenotype as Piezo1 and caveolae were often colocalized, and reduction of Cav-1 expression or disruption of caveolae with methyl-β-cyclodextrin led to not only reduced Piezo1 expression but also attenuation of the invasive phenotypes promoted by compressive stress. Taken together, our data indicate that mechanical compressive stress activates Piezo1 channels to mediate enhanced cancer cell invasion and matrix degradation that may be a critical mechanotransduction pathway during, and potentially a novel therapeutic target for, breast cancer metastasis.

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Section: Invasion Of Cells Through Layers Of Ecm Is a Critical Activisupporting

confidence: 87%

Compressive Stress Enhances Invasive Phenotype of Cancer Cells via Piezo1 Activation

Luo¹,

Ho²,

Tong³

et al. 2019

Preprint

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show abstract

“…16 Importantly, the proteolytic activity of MMPs can be also regulated by the endogenous TIMPs. 42,43 To clarify, we further analyzed the expression of TIMP-1 and TIMP-2 and the endogenous tissue inhibitors of MMPs, 44 and the data supported that the functional properties of MMPs and TIMPs are still balanced and scFv-M6-1B9 intrabodies could not influence the enzyme-inhibitor interaction. Moreover, of the several MMPs involved in the extracellular matrix degradation, not only MMP-2 and MMP-9 45 but also the reversion-inducing cysteine-rich protein with Kazal motifs also regulates the activity of MMP-2, MMP-9 and membrane type 1-MMP in many cancer cell lines.…”

Section: Discussionmentioning

confidence: 65%

“…Moreover, of the several MMPs involved in the extracellular matrix degradation, not only MMP-2 and MMP-9 45 but also the reversion-inducing cysteine-rich protein with Kazal motifs also regulates the activity of MMP-2, MMP-9 and membrane type 1-MMP in many cancer cell lines. 42,46 Besides MMPs, the serine protease urokinase plasminogen activator is also an important factor in promoting cancer cell invasion and metastasis. 47 Evidence has demonstrated that EMMPRIN can upregulate the expression of urokinase plasminogen activator and induce its proteolytic activity in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2

et al. 2014

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Extracellular matrix metalloproteinase inducer (EMMPRIN) exhibits overexpression in various cancers and promotes cancer progression and metastasis via the interaction with its associated molecules. The scFv-M6-1B9 intrabody has a potential ability to reduce EMMPRIN cell surface expression. However, the subsequent effect of scFv-M6-1B9 intrabody-mediated EMMPRIN abatement on its related molecules, α3β1-integrin, MCT1, MMP-2 and MMP-9, is undefined. Our results demonstrated that the scFv-M6-1B9 intrabody efficiently decreased α3β1-integrin cell surface expression levels. In addition, intracellular accumulation of MCT1 and lactate were increased. These results lead to suppression of features characteristic for tumor progression, including cell migration, proliferation and invasion, in a colorectal cancer cell line (Caco-2) although there was no difference in MMP expression. Thus, EMMPRIN represents an attractive target molecule for the disruption of cancer proliferation and metastasis. An scFv-M6-1B9 intrabody-based approach could be relevant for cancer gene therapy.

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“…In addition to TIMP-1 and other endogenously produced molecules, tetracycline antibiotics act as MMP inhibitors. Doxycycline, a tetracycline antibiotic, downregulates the transcription of MMP-8 and -9 and inhibits the protease activity of the enzyme [21,22] by chelating the Zn 2+ and Ca 2+ ions needed for the enzymatic activity of MMPs [11,23]. This effect is independent of its antimicrobial effect, as seen in studies utilising chemically modified tetracyclines devoid of antimicrobial activity [21].…”

Section: Introductionmentioning

confidence: 97%

“…Doxycycline, a tetracycline antibiotic, downregulates the transcription of MMP-8 and -9 and inhibits the protease activity of the enzyme [21,22] by chelating the Zn 2+ and Ca 2+ ions needed for the enzymatic activity of MMPs [11,23]. This effect is independent of its antimicrobial effect, as seen in studies utilising chemically modified tetracyclines devoid of antimicrobial activity [21]. In clinical studies doxycycline has both been shown to reduce the concentrations and the activity of MMP-8 and -9 in chronic inflammatory states [24] as well as to relieve clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis – A randomised placebo-controlled pilot trial

Nukarinen

Tervahartiala

Valkonen

et al. 2015

Pharmacological Research

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Regulation of matrix metalloproteinase expression

Cited by 11 publications

References 70 publications

Compressive Stress Enhances Invasive Phenotype of Cancer Cells via Piezo1 Activation

Compressive Stress Enhances Invasive Phenotype of Cancer Cells via Piezo1 Activation

EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2

Targeting matrix metalloproteinases with intravenous doxycycline in severe sepsis – A randomised placebo-controlled pilot trial

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