Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FoxO3a nuclear-cytoplasmic pulsing dynamics in a mammary epithelial cell line following growth-factor treatment with varying ERK/AKT activation loads. Dataset 1 of 3: single-cell reporter measurements.

ABSTRACT:

SUBMITTER: Somponnat Sampattavanich, Bernhard Steiert, Bernhard Kramer

PROVIDER: LDS-1382 | LINCS | 2017-05-02

REPOSITORIES: LINCS

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	HMS_LINCS&file=LDS-1382.tar.gz	Other

Items per page:

1 - 1 of 1

Similar Datasets

FoxO3a nuclear-cytoplasmic pulsing dynamics in a mammary epithelial cell line following growth-factor treatment with varying ERK/AKT activation loads. Dataset 2 of 3: single-cell reporter pulsing metrics.

Project description: Not available

2017-05-02 | LDS-1383 | LINCS

FoxO3a nuclear-cytoplasmic pulsing dynamics in a mammary epithelial cell line following growth-factor treatment with varying ERK/AKT activation loads. Dataset 3 of 3: mean reporter pulsing metrics.

Project description: Not available

2017-05-02 | LDS-1384 | LINCS

PML-II regulates ERK and AKT signal activation and IFNα-induced cell death.

Project description:BackgroundThe requirement of promyelocytic leukaemia protein (PML) in interferon (IFN)-induced cell apoptosis is well-established. However, the exact mechanisms by which the multiple isoforms of PML protein participate in this process remain not well-understood. We previously demonstrated that PML isoform II (PML-II) positively regulates induced gene expression during a type I IFN response and evaluate here how PML-II contributes to IFNα-induced cell death.MethodsHeLa cells were transiently depleted of PML-II by siRNA treatment and the response of these cells to treatment with IFNα assessed by molecular assays of mRNA and proteins associated with IFN and apoptosis responses.ResultsIn HeLa cells, death during IFNα stimulation was reduced by prior PML-II depletion. PML-II removal also considerably decreased the induced expression of pro-apoptotic ISGs such as ISG54 (IFIT2), and substantially impaired or prevented expression of PUMA and TRAIL, proteins that are associated with the intrinsic and extrinsic apoptotic pathways respectively. Thirdly, PML-II depletion enhanced ERK and AKT pro-survival signaling activation suggesting that PML-II normally suppresses signaling via these pathways, and that lack of PML-II hence led to greater than normal activation of AKT signaling upon IFNα stimulation and consequently increased resistance to IFNα-induced apoptosis.ConclusionsThe positive contribution of PML-II to the expression of various IFNα-induced pro-apoptotic proteins and its inhibition of pro-survival signaling together provide a mechanistic explanation for reduced apoptosis under conditions of PML deficiency and may account for at least part of the role of PML as a tumor suppressor gene. Video Abstract.

| S-EPMC8252201 | biostudies-literature

ART3 regulates triple-negative breast cancer cell function via activation of Akt and ERK pathways.

Project description:Triple-negative breast cancers (TNBCs) are defined by lack of expressions of estrogen, progesterone, and ERBB2 receptors. Because biology of TNBC is poorly understood, no targeted therapy has been developed for this breast cancer subtype and chemotherapy is its only systemic treatment modality. In this study, we firstly determined that the expression of human ecto-ADP-ribosyltransferase 3 (ART3) is significantly associated with the basal-like breast cancer subgroup, which is largely overlapped with TNBC, through analyzing published data sets. We also found that ART3 protein is significantly overexpressed in human TNBC tumors tissue and cell lines through using immunohistochemistry and immunoblotting. Overexpression of ART3 in MDA-MB-231 breast cancer cells increased cell proliferation, invasion, and survival in vitro and growth of xenograft tumors. Conversely, knockdown of ART3 in breast cancer cells inhibited cell proliferation and invasion. In addition, we showed that ART 3 overexpression activated AKT and ERK in vitro and in xenograft tumors. Together, our findings demonstrate that ART3 is a critical TNBC marker with functional significance.

| S-EPMC5216820 | biostudies-literature

ERK phosphorylates p66shcA on Ser36 and subsequently regulates p27kip1 expression via the Akt-FOXO3a pathway: implication of p27kip1 in cell response to oxidative stress.

Project description:Mice deficient for p66shcA represent an animal model to link oxidative stress and aging. p66shcA is implicated in oxidative stress response and mitogenic signaling. Phosphorylation of p66shcA on Ser36 is critical for its function in oxidative stress response. Here we report the identification of ERK as the kinase phosphorylating p66shcA on Ser36. Activation of ERKs was necessary and sufficient for Ser36 phosphorylation. p66shcA interacted with ERK and was demonstrated to be a substrate for ERK, with Ser36 being the major phosphorylation site. Furthermore, in response to H2O2, inhibition of ERK activation repressed p66shcA-dependent phosphorylation of FOXO3a and the down-regulation of its target gene p27kip1. Down-regulation of p27 might promote cell survival, as p27 played a proapoptotic role in oxidative stress response. As a feedback regulation, Ser36 phosphorylated p66shcA attenuated H2O2-induced ERK activation, whereas p52/46shcA facilitated ERK activation, which required tyrosine phosphorylation of CH1 domain. p66shcA formed a complex with p52/46ShcA, which may provide a platform for efficient signal propagation. Taken together, the data suggest there exists an interplay between ERK and ShcA proteins, which modulates the expression of p27 and cell response to oxidative stress.

| S-EPMC1182309 | biostudies-literature

Integrin ?11 cytoplasmic tail is required for FAK activation to initiate 3D cell invasion and ERK-mediated cell proliferation.

Project description:Integrin ?11?1 is a collagen-binding integrin, which is receiving increasing attention in the context of wound healing and fibrosis. Although ?11?1 integrin displays similar collagen specificity to ?2?1 integrin, both integrins have distinct in vivo functions. In this context, the contribution of ?11 subunit cytoplasmic tail interactions to diverse molecular signals and biological functions is largely unknown. In the current study, we have deleted the ?11 cytoplasmic tail and studied the effect of this deletion on ?11 integrin function. Compared to wild-type cells, C2C12 cells expressing tail-less ?11 attached normally to collagen I, but formed fewer focal contacts. ?11-tail-less cells furthermore displayed a reduced capacity to invade and reorganize a 3D collagen matrix and to proliferate. Analysis of cell signaling showed that FAK and ERK phosphorylation was reduced in cells expressing tail-less ?11. Inhibition of ERK and FAK activation decreased ?11-mediated cell proliferation, whereas ?11-mediated cell invasion was FAK-dependent and occurred independently of ERK signaling. In summary, our data demonstrate that the integrin ?11 cytoplasmic tail plays a central role in ?11 integrin-specific functions, including FAK-dependent ERK activation to promote cell proliferation.

| S-EPMC6814791 | biostudies-literature

Dual inactivation of Akt and ERK by TIC10 signals Foxo3a nuclear translocation, TRAIL gene induction, and potent antitumor effects.

Project description:Recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an antitumor protein that is in clinical trials as a potential anticancer therapy but suffers from drug properties that may limit efficacy such as short serum half-life, stability, cost, and biodistribution, particularly with respect to the brain. To overcome such limitations, we identified TRAIL-inducing compound 10 (TIC10), a potent, orally active, and stable small molecule that transcriptionally induces TRAIL in a p53-independent manner and crosses the blood-brain barrier. TIC10 induces a sustained up-regulation of TRAIL in tumors and normal cells that may contribute to the demonstrable antitumor activity of TIC10. TIC10 inactivates kinases Akt and extracellular signal-regulated kinase (ERK), leading to the translocation of Foxo3a into the nucleus, where it binds to the TRAIL promoter to up-regulate gene transcription. TIC10 is an efficacious antitumor therapeutic agent that acts on tumor cells and their microenvironment to enhance the concentrations of the endogenous tumor suppressor TRAIL.

| S-EPMC4535715 | biostudies-literature

Rapid and sustained nuclear-cytoplasmic ERK oscillations induced by epidermal growth factor.

Project description:Although the ERK pathway has a central role in the response of cells to growth factors, its regulatory structure and dynamics are incompletely understood. To investigate ERK activation in real time, we expressed an ERK-GFP fusion protein in human mammary epithelial cells. On EGF stimulation, we observed sustained oscillations of the ERK-GFP fusion protein between the nucleus and cytoplasm with a periodicity of approximately 15 min. The oscillations were persistent (>45 cycles), independent of cell cycle phase, and were highly dependent on cell density, essentially disappearing at confluency. Oscillations occurred even at ligand doses that elicited very low levels of ERK phosphorylation, and could be detected biochemically in both transfected and nontransfected cells. Mathematical modeling revealed that negative feedback from phosphorylated ERK to the cascade input was necessary to match the robustness of the oscillation characteristics observed over a broad range of ligand concentrations. Our characterization of single-cell ERK dynamics provides a quantitative foundation for understanding the regulatory structure of this signaling cascade.

| S-EPMC2824491 | biostudies-literature

Icariside II induces cell cycle arrest and apoptosis in human glioblastoma cells through suppressing Akt activation and potentiating FOXO3a activity.

Project description:Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and currently chemotherapeutic options for GBM are very limited. Given the poor prognosis, the development of novel anti-GBM agents is quite urgent. Using two human glioma cells (U87 and A172 cells), we demonstrated that Icariside II (ICA II), an active flavonoid compound derived from Epimedium koreanum, could inhibit GBM cell growth in a dose dependent manner. Wound healing data suggested that ICA II also inhibited the migration of human glioma cells. Mechanistically, ICA II induced apoptosis and cell cycle arrest, and this cytotoxic effect was dependent on the reduction of Forkhead box O3a(FOXO3a) phosphorylation mediated by Akt and the enrichment of nuclear FOXO3a, which initiated the transcription of p21/p27. Importantly, the cytotoxic effect induced by ICA II could be reversed by silencing the expression of FOXO3a, suggesting the critical role of FOXO3a in this process. Taken together, we propose ICA II as a potential novel anti-GBM candidate with a mechanism of inhibiting cell proliferation and inducing apoptosis through suppressing Akt activation and potentiating FOXO3a activity.

| S-EPMC5446533 | biostudies-literature

Cell type-specific activation of AKT and ERK signaling pathways by small negatively-charged magnetic nanoparticles.

Project description:The interaction of nanoparticles (NPs) with living organisms has become a focus of public and scientific debate due to their potential wide applications in biomedicine, but also because of unwanted side effects. Here, we show that superparamagnetic iron oxide NPs (SPIONs) with different surface coatings can differentially affect signal transduction pathways. Using isogenic pairs of breast and colon derived cell lines we found that the stimulation of ERK and AKT signaling pathways by SPIONs is selectively dependent on the cell type and SPION type. In general, cells with Ras mutations respond better than their non-mutant counterparts. Small negatively charged SPIONs (snSPIONs) activated ERK to a similar extent as epidermal growth factor (EGF), and used the same upstream signaling components including activation of the EGF receptor. Importantly, snSPIONs stimulated the proliferation of Ras transformed breast epithelial cells as efficiently as EGF suggesting that NPs can mimic physiological growth factors.

| S-EPMC3499776 | biostudies-literature