Dexamethasone suppresses α integrin expression by cytotrophoblasts

AbstractWnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs) formation. We found here, that Wnt5A regulates differently the expression of its receptors in the stable Wnt5A overexpressing clones. The expression levels of Frizzled (FZD)-2 and -5, were increased in different clones. However ROR-1, -2 expression levels were differently regulated in clones. Wnt5A overexpressing clones showed increased cell proliferation, migration, and clonogenicity. Moreover, Wnt5A overexpressing SKOV-3 clone showed increased MCAs formation ability. Cell invasion had been increased in OVCAR-3-derived clones, while this was decreased in SKOV-3-derived clone. Importantly, αv integrin expression levels were increased in all assessed clones, accompanied by increased cell attachment to fibronectin and focal adhesion kinase activity. Moreover, the treatment of clones with Box5 as a Wnt5A/FZD5 antagonist abrogates ITGAV increase, cell proliferation, migration, and their attachment to fibronectin. Accordingly, we observed significantly higher expression levels of ITGAV and ITGB3 in human high-grade serous ovarian cancer specimens and ITGAV correlated positively with Wnt5A in metastatic serous type ovarian cancer. In summary, we hypothesize here, that Wnt5A/FZD-5 signaling modulate αv integrin expression levels that could be associated with ovarian cancer cell proliferation, migration, and fibronectin attachment.

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Integrin Expression in Head and Neck Cancers

Acta Oto-Laryngologica ◽

10.3109/00016489509139322 ◽

1995 ◽

Vol 115 (2) ◽

pp. 328-330 ◽

Cited By ~ 7

Author(s):

G. Cortesina ◽

M. Sacchi ◽

M. Bussi ◽

B. Panizzut ◽

S. Ferro ◽

...

Keyword(s):

Head And Neck ◽

Head And Neck Cancers ◽

Integrin Expression

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Absence of the αvβ3 Integrin Dictates the Time-Course of Angiogenesis in the Hypoxic Central Nervous System: Accelerated Endothelial Proliferation Correlates with Compensatory Increases in α5β1 Integrin Expression

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2009.276 ◽

2010 ◽

Vol 30 (5) ◽

pp. 1031-1043 ◽

Cited By ~ 27

Author(s):

Longxuan Li ◽

Jennifer V Welser ◽

Richard Milner

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Time Course ◽

Αvβ3 Integrin ◽

Integrin Expression ◽

Brain Endothelial Cells ◽

Endothelial Proliferation ◽

Β3 Integrin ◽

Α5β1 Integrin

Cerebral angiogenesis is an important adaptive response to hypoxia. As the αvβ3 integrin is induced on angiogenic vessels in the ischemic central nervous system (CNS), and the suggested angiogenic role for this integrin in other systems, it is important to determine whether the αvβ3 integrin is an important mediator of cerebral angiogenesis. αvβ3 integrin expression was examined in a model of cerebral hypoxia, in which mice were subject to hypoxia (8% O2) for 0, 4, 7, or 14 days. Immunofluorescence and western blot analysis revealed that in the hypoxic CNS, αvβ3 integrin was strongly induced on angiogenic brain endothelial cells (BEC), along with its ligand vitronectin. In the hypoxia model, β3 integrin-null mice showed no obvious defect in cerebral angiogenesis. However, early in the angiogenic process, BEC in these mice showed an increased mitotic index that correlated closely with increased α5 integrin expression. In vitro experiments confirmed α5 integrin upregulation on β3 integrin-null BEC, which also correlated with increased BEC proliferation on fibronectin. These studies confirm hypoxic induction of αvβ3 integrin on angiogenic vessels, but suggest distinct roles for the BEC integrins αvβ3 and α5β1 in cerebral angiogenesis, with αvβ3 having a nonessential role, and α5β1 promoting BEC proliferation.

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β1 integrin expression by podocytes is required to maintain glomerular structural integrity

Developmental Biology ◽

10.1016/j.ydbio.2008.01.022 ◽

2008 ◽

Vol 316 (2) ◽

pp. 288-301 ◽

Cited By ~ 117

Author(s):

Ambra Pozzi ◽

George Jarad ◽

Gilbert W. Moeckel ◽

Sergio Coffa ◽

Xi Zhang ◽

...

Keyword(s):

Structural Integrity ◽

Β1 Integrin ◽

Integrin Expression

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Induction of β3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf–MEK–Extracellular Signal-Regulated Kinase Signaling Pathway

Molecular and Cellular Biology ◽

10.1128/mcb.21.9.3192-3205.2001 ◽

2001 ◽

Vol 21 (9) ◽

pp. 3192-3205 ◽

Cited By ~ 94

Author(s):

Douglas Woods ◽

Holly Cherwinski ◽

Eleni Venetsanakos ◽

Arun Bhat ◽

Stephan Gysin ◽

...

Keyword(s):

Cell Surface ◽

Signaling Pathway ◽

Erk Signaling ◽

Integrin Expression ◽

3T3 Cells ◽

Extracellular Signal ◽

Integrin Gene ◽

Β3 Integrin ◽

Nih 3T3 ◽

Nih 3T3 Cells

ABSTRACT Alterations in the expression of integrin receptors for extracellular matrix (ECM) proteins are strongly associated with the acquisition of invasive and/or metastatic properties by human cancer cells. Despite this, comparatively little is known of the biochemical mechanisms that regulate the expression of integrin genes in cells. Here we demonstrate that the Ras-activated Raf–MEK–extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines. Pharmacological inhibition of MEK1 in a number of human melanoma and pancreatic carcinoma cell lines led to reduced cell surface expression of α6- and β3-integrin. Consistent with this, conditional activation of the Raf-MEK-ERK pathway in NIH 3T3 cells led to a 5 to 20-fold induction of cell surface α6- and β3-integrin expression. Induced β3-integrin was expressed on the cell surface as a heterodimer with αv-integrin; however, the overall level of αv-integrin expression was not altered by Ras or Raf. Raf-induced β3-integrin was observed in primary and established mouse fibroblast lines and in mouse and human endothelial cells. Consistent with previous reports of the ability of the Raf-MEK-ERK signaling pathway to induce β3-integrin gene transcription in human K-562 erythroleukemia cells, Raf activation in NIH 3T3 cells led to elevated β3-integrin mRNA. However, unlike immediate-early Raf targets such as heparin binding epidermal growth factor and Mdm2, β3-integrin mRNA was induced by Raf in a manner that was cycloheximide sensitive. Surprisingly, activation of the Raf-MEK-ERK signaling pathway by growth factors and mitogens had little or no effect on β3-integrin expression, suggesting that the expression of this gene requires sustained activation of this signaling pathway. In addition, despite the robust induction of cell surface αvβ3-integrin expression by Raf in NIH 3T3 cells, such cells display decreased spreading and adhesion, with a loss of focal adhesions and actin stress fibers. These data suggest that oncogene-induced alterations in integrin gene expression may participate in the changes in cell adhesion and migration that accompany the process of oncogenic transformation.

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