Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration

Kataoka, Hiroaki; Itoh, Hiroshi; Koono, Masashi

doi:10.1046/j.1440-1827.2002.01320.x

Cited by 33 publications

(27 citation statements)

References 123 publications

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“…Consistent with the previous results, Sj7170 shares the similar structural characteristic with Ascaris-type SPIs. 5 Tumor progression is generally associated with extensive tissue remodeling to provide a proper environment for tumor growth, angiogenesis, invasion, and metastasis of cancer cells. An impressive amount of data reveals that, among many factors, proteases expressed by cancer cells are key players in this process.…”

Section: Discussionmentioning

confidence: 99%

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Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom

Song

Gong

Hong

et al. 2014

Journal of Biological Chemistry

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Background: Sj7170 is a new peptide from scorpion venom. Results: Sj7170 specifically inhibits the activity of ␣-chymotrypsin. Sj7170 promotes glioblastoma tumorigenesis and metastasis by up-regulating cyclin D1 and Snail. Conclusion: Sj7170 not only specifically inhibits ␣-chymotrypsin activity but also promotes the tumorigenesis and metastasis of glioblastoma. Significance: Sj7170 is a unique dual-function peptide with a protease inhibitory activity and a potent tumor-activating effect.

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Section: Discussionmentioning

confidence: 99%

“…Its expression was absent in five of the nine investigated high grade glioma cell lines (4). SPIs are often overexpressed in different tumor types, suggesting that the overexpression of these inhibitors might favor tumor progression (5).…”

mentioning

confidence: 97%

Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom

Song

Gong

Hong

et al. 2014

Journal of Biological Chemistry

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“…Therefore, inhibition of proteolytic activity as a result of various kinds of proteinase-proteinase inhibitor interactions is an important aspect of tumor cell biology. Serpins such as maspin, AAT, a 1 -antichymotrypsin, and Kunitz-type inhibitors such as urinary trypsin inhibitor (39) have been previously implicated in suppression of cancer invasion. It has been reported that cultured human tumor cell lines produce serine protease inhibitors, including AAT, which may play a role in controlling tumor growth and invasion by regulating activity of specific enzymes.…”

Section: Resultsmentioning

confidence: 99%

α₁-Antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain In Vitro

Janciauskiene¹,

Nita²,

Subramaniyam³

et al. 2008

Am J Respir Cell Mol Biol

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Matriptase is a type II transmembrane protease that is characterized by an N-terminal transmembrane and multiple extracellular domains, in addition to the conserved extracellular serine protease catalytic domain. The expression pattern of matriptase suggests that this protease may play broad roles in the biology of surface lining epithelial cells. In this study we report that a 1 -antitrypsin (AAT), an endogenous inhibitor of serine proteases, inhibits the catalytic domain of human recombinant matriptase in vitro. Co-incubation of AAT with matriptase (at a molar ratio 1:2) resulted in the formation of heat stable complexes, clearly seen in sodium dodecyl sulfate electrophoresis and Western blots. AAT was found to be a slow, tight-binding inhibitor of the catalytic domain of matriptase with a second order reaction rate constant of 0.31 3 10 3 M 21 s 21 . Notably, the oxidized form of AAT, which lacks serine protease inhibitor activity, failed to generate matriptase complexes and to inhibit matriptase activity. Since matriptase is involved in a number of physiologic processes, including activation of epithelial sodium channels, our findings offer considerable new insights into new regulatory function of AAT in vivo.

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“…HAI-1/SPINT1 is composed of an extracellular domain containing an NH 2 -terminal Kunitz domain (KD1), a low-density lipoprotein receptor (LDLR)-like domain and a COOH-terminal Kunitz domain (KD2), followed by a transmembrane region and a short cytoplasmic domain (3,4). To date, only a few examples of membrane-associated serine proteinase inhibitors have been reported (4,5), and HAI-1/SPINT1 seems to have in vivo roles that are both unique and important (6). Previous studies showed that HAI-1/SPINT1 potently inhibits the action of a variety of trypsin-like serine proteinases that may be involved in carcinogenesis, invasion, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte Growth Factor Activator Inhibitor Type 1 Regulates Epithelial to Mesenchymal Transition through Membrane-Bound Serine Proteinases

et al. 2009

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Hepatocyte growth factor activator inhibitor-1 (HAI-1), encoded by the serine protease inhibitor Kunitz type 1 (SPINT1) gene, is a membrane-associated proteinase inhibitor that potently inhibits a variety of serine proteinases, including those that are membrane bound. Although HAI-1/SPINT1 is widely expressed by epithelial cells and cancer cells, its functional role is still unclear, particularly in cancer. Here, we show that stable knockdown of HAI-1/SPINT1 in the human pancreatic cancer cell line SUIT-2 induces an elongated spindle-like morphology associated with accelerated invasion, thereby mimicking an epithelial to mesenchymal transition (EMT). We found that HAI-1/SPINT1 knockdown significantly reduced the expression of E-cadherin and was accompanied by up-regulation of Smad-interacting protein 1 (SIP1), an E-cadherin transcriptional repressor. In addition, matrix metalloproteinase-9 (MMP-9) was up-regulated. Similar results were obtained in the HLC-1 lung carcinoma cell line. Moreover, a metastatic variant of SUIT-2 (S2-CP8) that showed loss of E-cadherin expression also showed a significantly reduced level of HAI-1/SPINT1. Engineered overexpression of HAI-1/SPINT1 in S2-CP8 resulted in reversion of E-cadherin expression and SIP1 down-regulation, which accompanied reestablishment of epithelial morphology in culture. The EMT caused by HAI-1/SPINT1 knockdown seemed to be mediated, at least partly, by membrane-bound serine proteinases, matriptase/ST14 and TMPRSS4, as knockdown of matriptase/ST14 or TMPRSS4 in HAI-1/SPINT1 knockdown SUIT-2 cells and HLC-1 cells resulted in reversion of SIP1 and/or MMP-9 expression levels. We suggest that interactions between HAI-1/SPINT1 and membrane-bound serine proteinases contribute to transcriptional and functional changes involved in EMT in certain carcinoma cells.

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Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration

Cited by 33 publications

References 123 publications

Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom

Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom

α₁-Antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain In Vitro

Hepatocyte Growth Factor Activator Inhibitor Type 1 Regulates Epithelial to Mesenchymal Transition through Membrane-Bound Serine Proteinases

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Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration

Cited by 33 publications

References 123 publications

Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom

Sj7170, a Unique Dual-function Peptide with a Specific α-Chymotrypsin Inhibitory Activity and a Potent Tumor-activating Effect from Scorpion Venom

α1-Antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain In Vitro

Hepatocyte Growth Factor Activator Inhibitor Type 1 Regulates Epithelial to Mesenchymal Transition through Membrane-Bound Serine Proteinases

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α₁-Antitrypsin Inhibits the Activity of the Matriptase Catalytic Domain In Vitro