Prostate‐specific antigen activates single‐chain urokinase‐type plasminogen activator

Yoshida, Etsuo; Ohmura, Sayuri; Sugiki, Masahiko; Maruyama, Masugi; Mihara, Hisashi

doi:10.1002/ijc.2910630618

Cited by 55 publications

(40 citation statements)

References 22 publications

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“…For instance, PSA has the capacity to cleave extracellular matrix glycoproteins such as fibronectin and laminin and facilitate prostate cancer cell invasion (39). PSA can cleave and activate the urokinase-type plasminogen activator, which enhances tumor cell invasion (40). In prostate cancers, HIF-1 might cooperate with the AR to activate the expression of PSA and then facilitate prostate cancer invasion and progression.…”

Section: Discussionmentioning

confidence: 99%

Androgen-Dependent Gene Expression of Prostate-Specific Antigen Is Enhanced Synergistically by Hypoxia in Human Prostate Cancer Cells

Horii

Suzuki

Kondo

et al. 2007

Molecular Cancer Research

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The androgen receptor (AR) is implicated in prostate cancer growth, progression, and angiogenesis. Hypoxia-inducible factor-1 (HIF-1), which transcriptionally regulates hypoxia-inducible angiogenic factors, is up-regulated in prostate cancers compared with adjacent normal tissues. HIF-1 may be involved in prostate cancer as well as the AR, but the involvement of HIF-1 in prostate cancer angiogenesis and progression has not been fully elucidated. In the present study, we found that in prostate cancer LNCaP cells dihydrotestosterone enhanced the expression of GLUT-1, one of the HIF-1 target genes, and also that hypoxia enhanced the expression of prostate-specific antigen (PSA) that is one of the AR target genes and is involved in tumor invasion. Small interfering RNA that specifically inhibits HIF-1 reduced the expression levels of PSA as well as GLUT-1. Reporter gene analysis showed that dihydrotestosterone activated the HIF-1 -mediated gene expression and hypoxia enhanced the AR-induced promoter activity of human PSA gene. Deletion and site-directed mutation of the 5 ¶-flanking region of human PSA gene revealed that the sequence ACGTG between À3951 and À3947 was essential in the response to hypoxia. Furthermore, chromatin immunoprecipitation assay indicated that HIF-1 interacts with the AR on the human PSA gene promoter. These results indicated that in prostate cancers, HIF-1 might cooperate with the AR to activate the expression of several genes related to tumor angiogenesis, invasion, and progression. (Mol Cancer Res 2007;5(4):383 -91)

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Section: Discussionmentioning

confidence: 99%

Androgen-Dependent Gene Expression of Prostate-Specific Antigen Is Enhanced Synergistically by Hypoxia in Human Prostate Cancer Cells

Horii

Suzuki

Kondo

et al. 2007

Molecular Cancer Research

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“…Other enzymes have also been reported to activate sc-uPA, including plasma kallikrein (35), cathepsin B (36), cathepsin L (37), mast cell tryptase (38), and prostate-specific antigen (39). In these studies, sc-uPA was activated using a substrate to enzyme ratio of 30:1, 10:1, 200:1, 50:1, and 10:1, respectively.…”

Section: Characterization Of Mt-sp1 and Identification Of Substratesmentioning

confidence: 99%

Cellular Localization of Membrane-type Serine Protease 1 and Identification of Protease-activated Receptor-2 and Single-chain Urokinase-type Plasminogen Activator as Substrates

Takeuchi¹,

Harris²,

Huang³

et al. 2000

Journal of Biological Chemistry

399

369

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Membrane-type serine protease 1 (MT-SP1) was recently cloned, and we now report its biochemical characterization. MT-SP1 is predicted to be a type II transmembrane protein with an extracellular protease domain. This localization was experimentally verified using immunofluorescent microscopy and a cell-surface biotinylation technique. The substrate specificity of MT-SP1 was determined using a positional scanning-synthetic combinatorial library and substrate phage techniques. The preferred cleavage sequences were found to be (P4-(Arg/Lys)P3-(X)P2-(Ser)P1-(Arg)P1-(Ala)) and (P4-(X)P3-(Arg/Lys)P2-(Ser)P1(Arg) P1(Ala)), where X is a non-basic amino acid. Protease-activated receptor 2 (PAR2) and single-chain urokinase-type plasminogen activator are proteins that are localized to the extracellular surface and contain the preferred MT-SP1 cleavage sequence. The ability of MT-SP1 to activate PARs was assessed by exposing PAR-expressing Xenopus oocytes to the soluble MT-SP1 protease domain. The latter triggered calcium signaling in PAR2-expressing oocytes at 10 nM but failed to trigger calcium signaling in oocytes expressing PAR1, PAR3, or PAR4 at 100 nM. Singlechain urokinase-type plasminogen activator was activated using catalytic amounts of MT-SP1 (1 nM), but plasminogen was not cleaved under similar conditions. The membrane localization of MT-SP1 and its affinity for these key extracellular substrates suggests a role of the proteolytic activity in regulatory events.

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“…However, the level of active uPA is not reduced in the urine of mice bearing a targeted disruption of the plasminogen gene (17), suggesting the existence of plasmin-independent pro-uPA activation. Plasma kallikrein (18), trypsin-like proteases from human ovarian tumors (19), a T cell-associated serine protease (20), cathepsins B and L (21,22), nerve growth factor ␥ (23), human mast cell tryptase (24), and prostate-specific antigen (25) have also been reported to activate pro-uPA. However, the relevance of these studies of pro-uPA activation in vitro is uncertain for understanding roles of these enzymes in vivo.…”

Section: Matriptase Selectively Cleaves Peptide After An Arg or Lysmentioning

confidence: 99%

Activation of Hepatocyte Growth Factor and Urokinase/Plasminogen Activator by Matriptase, an Epithelial Membrane Serine Protease

Lee¹,

Dickson

Lin

2000

Journal of Biological Chemistry

366

362

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Matriptase is an epithelial-derived, integral membrane serine protease. The enzyme was initially isolated from human breast cancer cells and has been implicated in breast cancer invasion and metastasis. In the current study, using active matriptase isolated from human milk, we demonstrate that matriptase is able to cleave various synthetic substrates with arginine or lysine as their P1 sites and prefers small side chain amino acids, such as Ala and Gly, at P2 sites. For the most reactive substrates, N-tert-butoxycarbonyl (N-t-Boc)-␥-benzylGlu-Ala-Arg-7-amino-4-methylcoumarin (AMC) and N-tBoc-Gln-Ala-Arg-AMC, the K m values were determined to be 3.81 and 4.89 M, respectively. We further demonstrated that matriptase can convert hepatocyte growth factor/scattering factor to its active form, which can induce scatter of Madin-Darby canine kidney epithelial cells and can activate c-Met tyrosine phosphorylation in A549 human lung carcinoma cells. In addition, we noted that matriptase can activate urokinase plasminogen activator but has no affect on plasminogen. These results suggest that matriptase could act as an epithelial, upstream membrane activator to recruit and activate stromal-derived downstream effectors important for extracellular matrix degradation and epithelial migration, two major events of tissue remodeling, cancer invasion, and metastasis.

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Prostate‐specific antigen activates single‐chain urokinase‐type plasminogen activator

Cited by 55 publications

References 22 publications

Androgen-Dependent Gene Expression of Prostate-Specific Antigen Is Enhanced Synergistically by Hypoxia in Human Prostate Cancer Cells

Androgen-Dependent Gene Expression of Prostate-Specific Antigen Is Enhanced Synergistically by Hypoxia in Human Prostate Cancer Cells

Cellular Localization of Membrane-type Serine Protease 1 and Identification of Protease-activated Receptor-2 and Single-chain Urokinase-type Plasminogen Activator as Substrates

Activation of Hepatocyte Growth Factor and Urokinase/Plasminogen Activator by Matriptase, an Epithelial Membrane Serine Protease

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