6 research outputs found
Stress induces remodelling of yeast interaction and co-expression networks
Network analysis provides a powerful framework for the interpretation of genome-wide data. While static network approaches have proved fruitful, there is increasing interest in the insights gained from the analysis of cellular networks under different conditions. In this work, we study the effect of stress on cellular networks in fission yeast. Stress elicits a sophisticated and large scale cellular response, involving a shift of resources from cell growth and metabolism towards protection and maintenance. Previous work has suggested that these changes can be appreciated at the network level. In this paper, we study two types of cellular networks: gene co-regulation networks and weighted protein interaction networks. We show that in response to oxidative stress, the co-regulation networks re-organize towards a more modularised structure: while sets of genes become more tightly co-regulated, co-regulation between these modules is decreased. This shift translates into longer average shortest path length, increased transitivity, and decreased modular overlap in these networks. We also find a similar change in structure in the weighted protein interaction network in response to both oxidative stress and nitrogen starvation, confirming and extending previous findings. These changes in network structure could represent an increase in network robustness and/or the emergence of more specialised functional modules. Additionally, we find stress induces tighter co-regulation of non-coding RNAs, decreased functional importance of splicing factors, as well as changes in the centrality of genes involved in chromatin organization, cytoskeleton organization, cell division, and protein turnover
Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing’s syndrome
Knockdown of Ron Kinase Inhibits Mutant Phosphatidylinositol 3-Kinase and Reduces Metastasis in Human Colon Carcinoma*
Abnormal accumulation and activation of receptor tyrosine kinase Ron
(recepteur d'origine nantais) has been demonstrated in a variety of primary
human cancers. We show that RNA interference-mediated knockdown of Ron kinase
in a highly tumorigenic colon cancer cell line led to reduced proliferation as
compared with the control cells. Decreased Ron expression sensitized HCT116
cells to growth factor deprivation stress-induced apoptosis as reflected by
increased DNA fragmentation and caspase 3 activation. In addition, cell
motility was decreased in Ron knockdown cells as measured by wound healing
assays and transwell assays. HCT116 cells are heterozygous for gain of
function mutant PIK3CA H1047R. Analysis of signaling proteins that
are affected by Ron knockdown revealed that phosphatidylinositol 3-kinase
(PI3K) activity of the mutant PI3K as well as AKT phosphorylation was
substantially reduced in the Ron knockdown cells compared with the control
cells. Moreover, we demonstrated in vivo that knockdown of Ron
expression significantly reduced lung metastasis as compared with the control
cells in the orthotopic models. In summary, our results demonstrate that Ron
plays an essential role in maintaining malignant phenotypes of colon cancer
cells through regulating mutant PI3K activity. Therefore, targeting Ron kinase
could be a potential strategy for colon cancer treatment, especially in
patients bearing gain of function mutant PI3K activity