Matrix Metalloproteinases 9 and 10 Inhibit Protein Kinase C–Potentiated, p53-Mediated Apoptosis

Meyer, Éric; Vollmer, Jean-Yves; Bovey, R; Stamenkovic, Ivan

doi:10.1158/0008-5472.can-04-2908

Cited by 60 publications

(61 citation statements)

References 52 publications

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“…Mitotic phases are accompanied by a highly conserved and dynamic distribution of the enzyme as from studies in neuroblastoma cells and in macrophages (Sans-Fons et al, 2010;Ganji et al, 2011). Furthermore, MMP-9 affects apoptosis by degrading apoptotic molecules, as the Kit-ligand, hence promoting cells survival (Meyer et al, 2005). In addition, MMP-9 shedding of ICAM-1 confers protection to NK and Tcell mediated cytotoxicity (Fiore et al, 2002).…”

Section: Biological Aspectsmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Section: Biological Aspectsmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

209

212

View full text Add to dashboard Cite

show abstract

“…Thus, high expression of MMP-2 and MMP-9 may be used to characterize the behaviors of colorectal carcinoma (38,39). Moreover, high colorectal MMP-9 expression has been implicated in lung metastases (40) and tumor cell resistance to proapoptotic and p53 effects, as well as poor efficacy in postoperative adjuvant chemotherapy (41). In vitro, MIF also was shown to promote cell invasiveness through macrophage secretion of MMP (42).…”

Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 99%

Macrophage Migration Inhibitory Factor Promotes Colorectal Cancer

Chen

Yang

et al. 2009

Mol Med

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A growing body of evidence implicates macrophage migration inhibitory factor (MIF) in tumorigenesis and metastasis. In this study, we investigated whether MIF expression was associated with clinicopathologic features of colorectal carcinoma (CRC), especially in tumors with hepatic metastasis, and whether neutralization of endogenous MIF using anti-MIF therapeutics would inhibit tumor growth and/or decrease the frequency of colorectal hepatic metastases in a mouse colon carcinoma model. The concentration of serum MIF was positively correlated with an increased risk of hepatic metastasis in human patients with CRC (R = 1.25, 95% confidence internal = 1.02-1.52, P = 0.03). MIF was also dramatically upregulated in human colorectal tissue, with 20-40 times as many MIF-positive cells found in the mucosa of patients with CRC than in normal tissue (P < 0.001 ANOVA). Moreover, in those patients with metastatic colorectal cancer in the liver, MIF-positive cells were similarly increased in the diseased hepatic tissue. This increased MIF expression was restricted to diseased tissue and not found in areas of the liver with normal morphology. In subsequent in vitro experiments, we found that addition of recombinant MIF to colonic cell lines significantly increased their invasive properties and the expression of several genes (for example, matrix metalloproteinase 9 and vascular endothelial growth factor) known to be upregulated in cancerous tissue. Finally, we treated mice that had been given CT26 colon carcinoma cell transplants with anti-MIF therapeutics-either the MIF-specific inhibitor ISO-1 or neutralizing anti-MIF antibodies-and observed a significant reduction in tumor burden relative to vehicle-treated animals. Taken together, these data demonstrate that MIF expression was not only correlated with the presence of colorectal cancer but also may play a direct role in cancer development.

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“…Studies have demonstrated that PKC-d promotes cell death in many noncolonic cell lines, including keratinocytes (Denning et al, 1998), neutrophils (Pongracz et al, 1999), cerebral granule cells (Villalba, 1998), HL-60 and prostate cancer cells (Savickiene et al, 1999;Yin et al, 2005), but not in breast cancer cells (McCracken et al, 2003;Nabha et al, 2005). In studies in colonic cells, PKC signaling pathways are also involved in cell cycle and cell death regulation (Goldstein et al, 1995;Qiao et al, 1996;Sauma et al, 1996;Abraham et al, 1998;Perletti et al, 1998Perletti et al, , 1999Andre et al, 1999;Assert et al, 1999;Weller et al, 1999;Umar et al, 2000;Cerda et al, 2001;Lin et al, 2002;McMillan et al, 2003;Di Mari et al, 2005;Meyer et al, 2005). Several studies, including our own investigations, have demonstrated a tumor suppressor role for PKC-d in colon cancer cells, including cell cycle arrest and enhanced apoptosis (Weller et al, 1999;Cerda et al, 2001;Lin et al, 2002;McMillan et al, 2003;Perletti et al, 2004Perletti et al, , 2005.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase C delta inhibits Caco-2 cell proliferation by selective changes in cell cycle and cell death regulators

et al. 2006

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PKC-d is a serine/threonine kinase that mediates diverse signal transduction pathways. We previously demonstrated that overexpression of PKC-d slowed the G1 progression of Caco-2 colon cancer cells, accelerated apoptosis, and induced cellular differentiation. In this study, we further characterized the PKC-d dependent signaling pathways involved in these tumor suppressor actions in Caco-2 cells overexpressing PKC-d using a Zn 2 þ inducible expression vector. Consistent with a G1 arrest, increased expression of PKC-d caused rapid and significant downregulation of cyclin D1 and cyclin E proteins (50% decreases, Po0.05), while mRNA levels remained unchanged. The PKC agonist, phorbol 12-myristate 13-acetate (TPA, 100 nM, 4 h), induced two-fold higher protein and mRNA levels of p21 Waf1, a cyclin-dependent kinase (cdk) inhibitor in PKC-d transfectants compared with empty vector (EV) transfected cells, whereas the PKC-d specific inhibitor rottlerin (3 lM) or knockdown of this isoenzyme with specific siRNA oligonucleotides blocked p21Waf1 expression. Concomitantly, compared to EV control cells, PKC-d upregulation decreased cyclin D1 and cyclin E proteins co-immunoprecipitating with cdk6 and cdk2, respectively. In addition, overexpression of PKC-d increased binding of cdk inhibitor p27Kip1 to cdk4. These alterations in cyclin-cdks and their inhibitors are predicted to decrease G1 cyclin kinase activity. As an independent confirmation of the direct role PKC-d plays in cell growth and cell cycle regulation, we knocked down PKC-d using specific siRNA oligonucleotides. PKC-d specific siRNA oligonucleotides, but not irrelevant control oligonucleotides, inhibited PKCd protein by more than 80% in Caco-2 cells. Moreover, PKC-d knockdown enhanced cell proliferation (B1.4-2-fold, Po0.05) and concomitantly increased cyclin D1 and cyclin E expression (B1.7-fold, Po0.05). This was a specific effect, as nontargeted PKC-f was not changed by PKC-d siRNA oligonucleotides. Consistent with accelerated apoptosis in PKC-d transfectants, compared to EV cells, PKC-d upregulation increased proapoptotic regulator Bax two-fold at mRNA and protein levels, while antiapoptotic Bcl-2 protein was decreased by 50% at a post-transcriptional level. PKC-d specific siRNA oligonucleotides inhibited Bax protein expression by more than 50%, indicating that PKC-d regulates apoptosis through Bax. Taken together, these results elucidate two critical mechanisms regulated by PKC-d that inhibit cell cycle progression and enhance apoptosis in colon cancer cells. We postulate these antiproliferative pathways mediate an important tumor suppressor function for PKC-d in colonic carcinogenesis.

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Matrix Metalloproteinases 9 and 10 Inhibit Protein Kinase C–Potentiated, p53-Mediated Apoptosis

Cited by 60 publications

References 52 publications

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Macrophage Migration Inhibitory Factor Promotes Colorectal Cancer

Protein kinase C delta inhibits Caco-2 cell proliferation by selective changes in cell cycle and cell death regulators

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