Enhancement of fibroblast collagenase-1 (MMP-1) gene expression by tumor promoter okadaic acid is mediated by stress-activated protein kinases jun N-terminal kinase and p38

Westermarck, Jukka; Holmström, Tim H.; Ahonen, Matti; Eriksson, John E.; Kähäri, Veli‐Matti

doi:10.1016/s0945-053x(98)90107-x

Cited by 87 publications

(80 citation statements)

References 39 publications

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“…This observation is in agreement with recent studies with PD98059, demonstrating that ERK1,2 pathway mediates activation of MMP-1 expression in ®broblasts (Reunanen et al, 1998;Westermarck et al, 1998) and MMP-9 expression in transformed keratinocytes (Gum et al, 1997). Interestingly, a recent study demonstrated that IFN-g inhibits TGF-b signaling in ®brosarcoma cells by inducing expression of SMAD7, an inhibitory member of the SMAD transcription factor family (Ulloa et al, 1999).…”

Section: Discussionsupporting

confidence: 93%

“…In addition, overexpression of tissue inhibitor of metalloproteinases (TIMP)-1, -2, and -3 appears an e ective way of inhibiting the invasion of malignant cells . Our results together with recent observations (Reunanen et al, 1998;Ravanti et al, 1999;Westermarck et al, 1998;Gum et al, 1997) indicate that modulation of the activity of distinct MAPKs may serve as a potent way of inhibiting MMP expression and invasion. In conclusion, the results of the present study show that selective activation of the IFN-g signaling pathway may serve as a speci®c way of potently suppressing invasion and metastasis of malignant squamous epithelial cells in vivo.…”

Section: Discussionsupporting

confidence: 82%

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Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-γ is associated with activation of extracellular signal-regulated kinase-1,2 and STAT1

et al. 2000

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Collagenase-3 (MMP-13) is characterized by an exceptionally wide substrate speci®city and restricted expression. MMP-13 is speci®cally expressed by transformed human keratinocytes in squamous cell carcinomas in vivo and its expression correlates with their invasion capacity. Here, we show, that interferon-g (IFN-g) markedly inhibits expression of MMP-13 by human cutaneous SCC cells (UT-SCC-7) and by ras-transformed human epidermal keratinocytes (A-5 cells) at the transcriptional level. In addition, IFN-g inhibits collagenase-1 (MMP-1) expression in these cells. IFN-g abolished the enhancement of MMP-13 and MMP-1 expression by transforming growth factor-b (TGF-b) and tumor necrosis factor-a (TNF-a), and inhibited invasion of A-5 cells through type I collagen. IFN-g also rapidly and transiently activates extracellular signal-regulated kinase 1,2 (ERK1,2) and blocking ERK1,2 pathway (Raf/MEK1,2/ERK1,2) by speci®c MEK1,2 inhibitor PD98059 partially (by 50%) prevents Ser-727 phosphorylation of STAT1 and suppression of MMP-13 expression by IFN-g. Furthermore, Ser-727 phosphorylation of STAT1 by ERK1,2, or independently of ERK1,2 activation is associated with marked reduction in MMP-13 expression. These observations identify a novel role for IFN-g as a potent inhibitor of collagenolytic activity and invasion of transformed squamous epithelial cells, and show that inhibition of MMP-13 expression by IFN-g involves activation of ERK1,2 and STAT1. Oncogene (2000) 19, 248 ± 257.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 82%

Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-γ is associated with activation of extracellular signal-regulated kinase-1,2 and STAT1

et al. 2000

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“…The expression of various matrix metalloproteinases, which are responsible for tumor cell invasion, have been shown to be inhibited by the p38 MAPK specific inhibitor, SB203580. [32][33][34] The increased expression of urokinase-type plasminogen activator and its receptor (uPA and uPAR, respectively, believed to confer invasiveness of MDA-MB-231 cells) is sensitive to SB 203580 through message destabilization via adenylate-and uridylate-rich elements. 35 Finally, we compared the level of activity of the 3 MAPK members by probing Western immunoblots with antibodies recognizing the activated forms only.…”

Section: Resultsmentioning

confidence: 99%

Dysregulation of phosphatidylinositol 3‐kinase and downstream effectors in human breast cancer

Salh

Marotta

Wagey

et al. 2001

Intl Journal of Cancer

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Phosphatidylinositol 3-kinase (PI3-K) is a growth factoractivated transforming lipid (and protein) kinase, involved in cell motility and invasion, that has multiple effectors. Relatively little is known about its expression and enzymatic activity in human breast cancer. Since growth factor receptors are amplified in breast cancer, and the tumor suppressor PTEN may be mutated in human breast cancer, it was hypothesized that PI3-K and its downstream effectors would be activated in this disease. In 11 resected tumors analyzed for expression of this kinase, a mean 3-fold increase in protein expression was observed over the corresponding adjacent control tissue. Using an in vitro lipid kinase assay of the immunoprecipitated PI3-K protein, a greater than 2-fold increase in activation was observed. These changes were observed in the absence of an activation of either protein kinase B (PKB, akt1) or p70 S6 kinase (p70 S6K). However, p21-activated kinase (Pak), p38 mitogen-activated protein kinase (p38 MAPK) and mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK 2) were all overexpressed and demonstrated increased enzyme activity. It may be concluded that aberrant mitogenic signaling in human breast cancer in vivo involves Pak, p38 MAPK and MAPKAPK2 downstream of PI3-K, but neither of PKB or p70 S6K. It is proposed that this pathway may serve as a useful targeting nexus for investigation of small molecule inhibitors in human breast cancer.

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“…Tumour cells produce factors, which enhance production of MMPs by fibroblasts. 43,44 It is likely that MMPs form a network in which a single MMP cleaves certain native or partially degraded matrix components and activates other latent MMPs. It is also likely that distinct MMPs play a role at different stages of tumour development.…”

Section: Mmps In Tumor Invasionmentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

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580

484

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Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer.

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Enhancement of fibroblast collagenase-1 (MMP-1) gene expression by tumor promoter okadaic acid is mediated by stress-activated protein kinases jun N-terminal kinase and p38

Cited by 87 publications

References 39 publications

Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-γ is associated with activation of extracellular signal-regulated kinase-1,2 and STAT1

Inhibition of collagenase-3 (MMP-13) expression in transformed human keratinocytes by interferon-γ is associated with activation of extracellular signal-regulated kinase-1,2 and STAT1

Dysregulation of phosphatidylinositol 3‐kinase and downstream effectors in human breast cancer

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

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