p53 Inhibits Angiogenesis by Inducing the Production of Arresten

Assadian, Sarah; El-Assaad, Wissal; Wang, Xue Q.D.; Gannon, Phillipe O.; Barrès, Véronique; Latour, Mathieu; Mes-Masson, Anne-Marie; Saad, Fred; Sado, Yoshikazu; Dostie, Josée; Teodoro, Jose G.

doi:10.1158/0008-5472.can-11-2348

Cited by 64 publications

(43 citation statements)

References 38 publications

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“…P53 regulates expression of genes involved in both growth and apoptosis through activation of gene transcription and has a known role in activation of some CK (e.g. CK8 ) and collagen genes [25], [26].…”

Section: Resultsmentioning

confidence: 99%

Group B Streptococcal Infection of the Choriodecidua Induces Dysfunction of the Cytokeratin Network in Amniotic Epithelium: A Pathway to Membrane Weakening

Vanderhoeven

Bierle²,

Kapur

et al. 2014

PLoS Pathog

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Early events leading to intrauterine infection remain poorly defined, but may hold the key to preventing preterm delivery. To determine molecular pathways within fetal membranes (chorioamnion) associated with early choriodecidual infection that may progress to preterm premature rupture of membranes (PPROM), we examined the effects of a Group B Streptococcus (GBS) choriodecidual infection on chorioamnion in a nonhuman primate model. Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received choriodecidual inoculation of either GBS (n = 5) or saline (n = 5). Cesarean section was performed in the first week after GBS or saline inoculation. RNA extracted from chorioamnion (inoculation site) was profiled by microarray. Single gene, Gene Set, and Ingenuity Pathway Analysis results were validated using qRT-PCR (chorioamnion), Luminex (amniotic fluid, AF), immunohistochemistry, and transmission electron microscopy (TEM). Despite uterine quiescence in most cases, significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6) were detected in GBS versus controls (p<0.05). Choriodecidual infection resolved by the time of cesarean section in 3 of 5 cases and GBS was undetectable by culture and PCR in the AF. A total of 331 genes were differentially expressed (>2-fold change, p<0.05). Remarkably, GBS exposure was associated with significantly downregulated expression of multiple cytokeratin (CK) and other cytoskeletal genes critical for maintenance of tissue tensile strength. Immunofluorescence revealed highly significant changes in the CK network within amniocytes with dense CK aggregates and retraction from the cell periphery (all p = 0.006). In human pregnancies affected by PPROM, there was further evidence of CK network retraction with significantly shorter amniocyte foot processes (p = 0.002). These results suggest early choriodecidual infection results in decreased cellular membrane integrity and tensile strength via dysfunction of CK networks. Downregulation of CK expression and perturbations in the amniotic epithelial cell intermediate filament network occur after GBS choriodecidual infection, which may contribute to PPROM.

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Section: Resultsmentioning

confidence: 99%

Group B Streptococcal Infection of the Choriodecidua Induces Dysfunction of the Cytokeratin Network in Amniotic Epithelium: A Pathway to Membrane Weakening

Vanderhoeven

Bierle²,

Kapur

et al. 2014

PLoS Pathog

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“…p53 is an important tumor suppressor gene involved in DNA repair, cell cycle, tumor angiogenesis, and other biological processes (27,30,37,38). MDM2 is the most vital molecule regulating p53 concentration and activity and destroys p53 protein via ubiquitination.…”

Section: Discussionmentioning

confidence: 99%

The circadian clock gene PER2 plays an important role in tumor suppression through regulating tumor-associated genes in human oral squamous cell carcinoma

Chen

Yang

et al. 2017

Oncology Reports

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Abstract. Low expression of the clock gene PER2 is closely related to carcinogenesis and the development of cancer; however, the mechanism of the low expression of PER2 that led to cell malignant transformation remains unclear. This study used RNA interference (RNAi) technology to silence PER2 in SCC15 human oral squamous cell carcinoma (OSCC) cells. Then it was found that the ability of cancer cell proliferation, migration, and invasion were markedly increased (P<0.05), and the ability of cancer cell apoptosis and the number of cells in G1/G0 phase were markedly reduced (P<0.05) after PER2 knockdown. PER2 knockdown increased the expression of MDM2, MMP2, and VEGF mRNA (P<0.05), and decreased the expression of p53, Bax, and TIMP-2 mRNA (P<0.05). The in vivo experiments also proved that the tumorigenicity of SCC15 cells was significantly enhanced after PER2 silence (P<0.05). Overall, these results show that PER2 through the regulation of the numerous important downstream tumor-related genes, plays a major role in tumor suppression, and it may be a novel molecular target for cancer treatment.

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“…The soluble NC1 domain from α1-chain of type IV collagen (α1(IV)NC1 or arresten) is a known inhibitor of tumor angiogenesis, whose antiangiogenic actions are partly mediated through α1β1-integrin910212630314041. The antiangiogenic functions of this molecule are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE:Type IV collagen α1-chain noncollagenous domain blocks MMP-2 activation both in-vitro and in-vivo

Sudhakar

Verma

Pawar

2014

Sci Rep

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α1(IV)NC1 inhibits angiogenesis by regulating MAPK activation, this biological function was partly attributed α1(IV)NC1 binding to α1β1-integrin. However, its potent antiangiogenic activity and the molecular targets of α1(IV)NC1 has not been investigated. In the present study, the regulation of MMP-2 activation by α1(IV)NC1 was evaluated. α1β1-integrin which is required for inhibition of angiogenesis is not playing a role in cellular invasion and inhibition of MMP-2 activation by α1(IV)NC1. We found that α1(IV)NC1 binds the CBD of MMP-2 and forming a stable complex that prevents activation of MMP-2. The antiangiogenic activity of α1(IV)NC1 is mediated, in part, by this binding activity. In addition, up-regulation of TIMP-2 by α1(IV)NC1 led to saturation of MT1-MMP binding sites, which in turn led to inhibition of MMP-2 activation. In-vivo studies using α1-integrin null-mice treated with higher doses of α1(IV)NC1 showed integrin independent inhibition of tumor growth and active-MMP-2, without affecting MMP-9, MMP-7 and angiostatin.

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p53 Inhibits Angiogenesis by Inducing the Production of Arresten

Cited by 64 publications

References 38 publications

Group B Streptococcal Infection of the Choriodecidua Induces Dysfunction of the Cytokeratin Network in Amniotic Epithelium: A Pathway to Membrane Weakening

Group B Streptococcal Infection of the Choriodecidua Induces Dysfunction of the Cytokeratin Network in Amniotic Epithelium: A Pathway to Membrane Weakening

The circadian clock gene PER2 plays an important role in tumor suppression through regulating tumor-associated genes in human oral squamous cell carcinoma

RETRACTED ARTICLE:Type IV collagen α1-chain noncollagenous domain blocks MMP-2 activation both in-vitro and in-vivo

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