Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades

Gum, Rebecca J.; Wang, H; Lengyel, Ernst; Juarez, Jose; Boyd, Douglas D.

doi:10.1038/sj.onc.1200973

Cited by 221 publications

(176 citation statements)

References 42 publications

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“…These p38 MAPK and AP-1 expression, binding and transactivation SF Rosenberger et al modi®cations most likely in form of phosphorylation are mediated through an increase in ERK-1/2 activity which is required but apparently not su cient for increased transactivation. These data are consistent with a report by Gum et al (1997) demonstrating a requirement for both ERK-1/2 and JNK in AP-1 mediated collagenase expression.…”

Section: Discussionsupporting

confidence: 93%

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

1999

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By performing in vitro kinase assays we found in papilloma producing 308 mouse keratinocytes that okadaic acid elevated activities of extracellular signalregulated kinase (ERK) 1/2, c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinases (MAPKs). This okadaic acid mediated activation of MAP kinases correlated with increased AP-1 binding to a consensus TPA responsive element (TRE) and elevated TRE dependent transcription. To determine the role of p38 MAP kinases in these processes we employed the speci®c p38 MAP kinase inhibitor SB 203580. Using orthophosphate labeling we showed a decrease in phosphorylation of MAPK activated protein kinase-2 (MAPKAP-K2) indicating reduced activity of p38 MAPKs utilizing this kinase as substrate. In contrast, we found that SB 203580 raised activities of ERK-1/2 and JNKs. Electrophoretic mobility shift assays revealed an increase in TRE binding activity in response to SB 203580 most likely resulting from increased expression of the major TRE binding components JunD and FosB as indicated by Western blot analyses. Increased TRE DNA binding failed to lead to increased transactivation correlating with the inability of SB 203580 to increase phosphorylation of these AP-1 proteins. These data indicate that SB 203580 sensitive p38 MAP kinases are not involved in okadaic acid mediated increases in TRE DNA binding and transactivation.

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Section: Discussionsupporting

confidence: 93%

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

1999

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“…In addition, our data are consistent with mounting information (Silberman et al, 1997;Gum et al, , 1997Lengyel et al, 1996Lengyel et al, , 1997 indicating that mitogenic signaling pathways stimulate the upregulation of uPA and MMPs. In this regard, an understanding of the mechanism(s) that tumor cells use to become tumorigenic and govern the production of proteases, which apparently includes the RalA-PLD1 pathway, may prove to be an important target for therapeutic intervention in tumor progression.…”

Section: The Dominant Negative S28n Rala Mutant Prevents Vsrc and V-rsupporting

confidence: 91%

“…Signaling pathways activated by v-Src and v-Ras (Burgering and Bos, 1995) include those involving phosphatidylinositol-3-kinase (Carpenter and Cantley, 1996), protein kinase C (Song et al, 1991), Raf-1 (Blobe et al, 1994) the extracellular regulated kinases (ERK-1 and 2) (Burgering and Bos, 1995) and phospholipase D (PLD) (Song et al, 1991). It has been reported that Raf-1, MEK-1 and ERK1 mediate the signal leading to uPA, uPA receptor, and MMP-9 upregulation Gum et al, 1997). We recently reported that overexpression of uPA in murine mammary adenocarcinoma cells is controlled by a PLD and protein kinase C-dependent pathway (Aguirre Ghiso et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

RalA requirement for v-Src- and v-Ras-induced tumorigenicity and overproduction of urokinase-type plasminogen activator: involvement of metalloproteases

et al. 1999

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Overproduction of urokinase-type plasminogen activator (uPA) and metalloproteases (MMPs) is strongly correlated with tumorigenicity and with invasive and metastatic phenotypes of human and experimental tumors. We demonstrated previously that overproduction of uPA in tumor cells is mediated by a phospholipase D (PLD)-and protein kinase C-dependent mechanism. The oncogenic stimulus of v-Src and v-Ras results in the activation of PLD, which is dependent upon the monomeric GTPase RalA. We have therefore investigated whether RalA plays a role in uPA and MMP overproduction that is observed in response to oncogenic signals. We report here that NIH3T3 cells transformed by both v-Src and v-Ras, constitutively overproduce uPA and that expression of a dominant negative RalA mutant (S28N) blocks overproduction of uPA in both the v-Srcand v-Ras-transformed cells. v-Src and v-Ras also induced an upregulation of the activity of MMP-2 and MMP-9 as detected by zymograms, however only the vSrc induction correlated with MMP protein levels detected by Western blot analysis. The dominant negative RalA mutant blocked increased MMP-2 and 9 overproduction induced by v-Src, but not the increased activity of MMP-2 and 9 induced by v-Ras. And, consistent with a role for the RalA/PLD pathway in mitogenesis and tumor development, the dominant negative RalA mutant completely blocked tumor formation by v-Src-and v-Ras-transformed NIH3T3 cells injected subcutaneously in syngeneic mice. The data presented here implicate RalA and PLD as signaling mediators for tumor formation and protease production by transformed cells.

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“…MMP-9 production has been shown to be directly dependent on the activation of endogenous ERK signalling in hepatocyte growth factor-or epidermal growth factor-stimulated human epidermal keratinocytes (Zeigler et al, 1999). Induction of MMP-9 promoter activity by oncogenic Ras in squamous carcinoma cells has been shown to be abrogated by blocking the ERK 1/2 pathway (Gum et al, 1997). Increased transcriptional activity of the MMP-9 promoter in Ras-transformed ovarian carcinoma cells has also been shown to be mediated by MAP kinases (Gum et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Integrin αvβ6-associated ERK2 mediates MMP-9 secretion in colon cancer cells

Dorahy

et al. 2002

Br J Cancer

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There is general consensus that matrix metalloproteinases are involved in tumour progression. We show herein that inhibition of integrin avb6 expression in colon cancer cells suppresses MMP-9 secretion. This integrin-mediated event is dependent upon direct binding between the b6 integrin subunit and extracellular signal-regulated kinase 2. Targetting either b6 or its interaction with extracellular signal-regulated kinase in order to inhibit matrix metalloproteinase activity may offer a useful therapeutic approach in preventing growth and spread of colon cancer.

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Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades

Cited by 221 publications

References 42 publications

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

Inhibition of p38 MAP kinase increases okadaic acid mediated AP-1 expression and DNA binding but has no effect on TRE dependent transcription

RalA requirement for v-Src- and v-Ras-induced tumorigenicity and overproduction of urokinase-type plasminogen activator: involvement of metalloproteases

Integrin αvβ6-associated ERK2 mediates MMP-9 secretion in colon cancer cells

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