Raf kinase inhibitor protein positively regulates cell–substratum adhesion while negatively regulating cell–cell adhesion

Henry, Kevin T. Mc; Montesano, Roberto; Zhu, Shoutian; Beshir, Anwar B.; Tang, Hanmei; Yeung, Kam C.; Fenteany, Gabriel

doi:10.1002/jcb.21470

Cited by 28 publications

(28 citation statements)

References 83 publications

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“…Tight and adherens junction protein modifications can also occur without protease release. For example, overexpression of Raf kinase inhibitor protein in epithelial cells decreases cell-to-cell adhesion by affecting proteins that form the adherens and tight junctions between cells (15). In regard to endothelial cells, increased intracellular Ca 2ϩ , both released from internal stores and by movement of extracellular Ca 2ϩ into the cell, induces contraction of the cells via myosin light chain-dependent cytoskeleton retraction and the disassembly of interendothelial junctions (28).…”

Section: Discussionmentioning

confidence: 99%

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

McClenahan

Hillenbrand

Kapur

et al. 2009

Clin Vaccine Immunol

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Pneumonia in cattle is an important disease both economically and in terms of animal welfare. Recent evidence in other species has shown ATP to be an important modulator of inflammation in the lung, where it is released by activated alveolar macrophages and damaged lung cells. Whether ATP serves a similar process during infection in the bovine lung is unknown. In the present study, we examined the effects of ATP treatment on the morphology, apoptosis, and permeability of bovine pulmonary epithelial (BPE) cells and bovine pulmonary microvascular endothelial cells (BPMEC). Monolayers of BPE cells underwent striking morphological changes when exposed to ATP that included separation of the cells. Neither BPE cells nor BPMEC exhibited increased apoptosis in response to ATP. BPE cell and BPMEC monolayers displayed virtually identical increases in permeability when exposed to ATP, with a 50% change occurring within the first hour of exposure. Both cell types contained mRNA for the P2X 7 receptor, a known receptor for ATP. In BPE cells, but not BPMEC, the change in permeability in response to ATP was reversed by the addition of a P2X 7 receptor antagonist. If similar permeability changes occur in vivo, they could be a factor in vascular leakage into lung airspaces during pneumonia.Several infectious agents are involved in the bovine respiratory disease complex. Among the bacteria involved in this complex, Mannheimia haemolytica is associated with particularly severe lung inflammation that culminates in extensive lung pathology. One of the hallmark pathological changes associated with M. haemolytica pneumonia is the extensive leakage of vascular products into the lung interstitium and air spaces (24,30). We have previously demonstrated that lipopolysaccharide (LPS) can induce permeability changes in endothelial cells in vitro that would be consistent with vascular leakage. However, the effects are slow, requiring well over 12 h to cause measurable effects on permeability (13). It is possible that the host releases substances in the early pathological response that contribute to the extensive leakage of vascular products into the lung. One such possible substance is ATP.The involvement of extracellular ATP in lung inflammation is a relatively new area of research. Patients with cystic fibrosis, a chronic inflammatory lung disease in humans, have increased levels of ATP in both their sputum and lungs (4). This has been correlated with increased neutrophil numbers in the lung. In a model of asthma, extracellular ATP activated dendritic cells in the lungs, which then stimulated airway inflammation (6). Airway smooth muscle contraction, another physiologic change associated with asthma, is also stimulated by ATP (16). The effects of ATP are not always detrimental. ATP appears to have a protective effect in acute inflammation. Kolosova et al. demonstrated that a long-lasting, nonhydrolyzed form of ATP (ATP␥S) given to mice after transtracheal administration of LPS prevented increases in bronchoalveolar lavage protein and white...

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Section: Discussionmentioning

confidence: 99%

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

McClenahan

Hillenbrand

Kapur

et al. 2009

Clin Vaccine Immunol

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“…Alternatively, it could entail the ability of cells to degrade extracellular matrix (ECM) barriers, adhere in complex three-dimensional settings or some other process relevant to invasion and metastasis. While RKIP expression inversely correlates with cell movement in human hepatocellular carcinoma cells [26], RKIP instead appears to positively control the motility of Madin-Darby canine kidney (MDCK) epithelial cells and MCF7 human breast carcinoma cells [27–29], as well as rat hepatic stellate cells [30]. RKIP also regulates cell-substratum and cell-cell adhesion in MDCK cells [28,29].…”

Section: Introductionmentioning

confidence: 99%

Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression

Beshir¹,

Ren²,

Magpusao³

et al. 2010

Cancer Letters

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Accumulating evidence suggests that Raf kinase inhibitor protein (RKIP), which negatively regulates multiple signaling cascades including the Raf and nuclear factor κB (NF-κB) pathways, functions as a metastasis suppressor. However, the basis for this activity is not clear. We investigated this question in a panel of breast cancer, colon cancer and melanoma cell lines. We found that RKIP negatively regulated the invasion of the different cancer cells through three-dimensional extracellular matrix barriers by controlling the expression of matrix metalloproteinases (MMPs), particularly, MMP-1 and MMP-2. Silencing of RKIP expression resulted in a highly invasive phenotype and dramatically increased levels of MMP-1 and MMP-2 expression, while overexpression of RKIP decreased cancer cell invasion in vitro and metastasis in vivo of murine tumor allografts. Knockdown of MMP-1 or MMP-2 in RKIP-knockdown cells reverted their invasiveness to normal. In contrast, when examining migration of the different cancer cells in a two-dimensional, barrier-less environment, we found that RKIP had either a positive regulatory activity or no activity, but in no case a negative one (as would be expected if RKIP suppressed metastasis at the level of cell migration itself). Therefore, RKIP’s function as a metastasis suppressor appears to arise from its ability to negatively regulate expression of specific MMPs, and thus invasion through barriers, and not from a direct effect on the raw capacity of cells to move. The NF-κB pathway, but not the Raf pathway, appeared to positively control the invasion of breast cancer cells. A regulatory loop involving an opposing relationship between RKIP and the NF-κB pathway may control the level of MMP expression and cell invasion.

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“…RKIP was previously shown to be involved in preventing chromosomal abnormalities (39), preventing metastasis (21, 22) and promoting cell-substratum adhesion (40). More relevant to our study is the role of RKIP in the RAF/MEK/Erk and NF κ B pathways (35).…”

Section: Discussionmentioning

confidence: 99%

The Oxazolidinone Derivative Locostatin Induces Cytokine Appeasement

Ménoret

McAleer²,

Ngoi³

et al. 2009

The Journal of Immunology

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Damaging inflammation arising from autoimmune pathology and septic responses results in severe cases of disease. In both instances, anti-inflammatory compounds are used to limit the excessive or deregulated cytokine responses. We used a model of robust T cell stimulation to identify new proteins involved in triggering a cytokine storm. A comparative proteomic mining approach revealed the differential mapping of Raf kinase inhibitory protein after T cell recall in vivo. Treatment with locostatin, an Raf kinase inhibitory protein inhibitor, induced T cell anergy by blocking cytokine production after Ag recall. This was associated with a reduction in Erk phosphorylation. Importantly, in vivo treatment with locostatin profoundly inhibited TNF-α production upon triggering the Ag-specific T cells. This effect was not limited to a murine model because locostatin efficiently inhibited cytokine secretion by human lymphocytes. Therefore, locostatin should be a useful therapeutic to control inflammation, sepsis, and autoimmune diseases.

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Raf kinase inhibitor protein positively regulates cell–substratum adhesion while negatively regulating cell–cell adhesion

Cited by 28 publications

References 83 publications

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Effects of Extracellular ATP on Bovine Lung Endothelial and Epithelial Cell Monolayer Morphologies, Apoptoses, and Permeabilities

Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression

The Oxazolidinone Derivative Locostatin Induces Cytokine Appeasement

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