PubMed Journal Database | Oncogene 
The US National Library of Medicine and National Institutes of Health manage PubMed.gov which comprises of more than 21 million records, papers, reports for biomedical literature, including MEDLINE, life science and medical journals, articles, reviews, reports and books. BioPortfolio aims to publish relevant information on published papers, clinical trials and news associated with users selected topics.
For example view all recent relevant publications on Epigenetics and associated publications and clincial trials.
Showing PubMed Articles 1–25 of 854 from Oncogene
Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored durin...
ADAM12-cleaved ephrin-A1 contributes to lung metastasis.
Eph receptor tyrosine kinases and their ephrin ligands have been implicated in neuronal development and neovascularization. Overexpression of ephrin-A1 has been implicated in tumor progression and poor prognosis. However, the mechanisms are not clear. Here, we report a role of the Eph/ephrin system in a cell adhesion mechanism. Clustered erythropoietin-producing hepatocellular receptor A1 (EphA1)/ephrin-A1 complexes on the plasma membrane did not undergo endocytosis, and the cell remained adherent to one an...
Brd4 maintains constitutively active NF-κB in cancer cells by binding to acetylated RelA.
Acetylation of the RelA subunit of NF-κB at lysine-310 regulates the transcriptional activation of NF-κB target genes and contributes to maintaining constitutively active NF-κB in tumors. Bromodomain-containing factor Brd4 has been shown to bind to acetylated lysine-310 (AcLys310) and to regulate the transcriptional activity of NF-κB, but the role of this binding in maintaining constitutively active NF-κB in tumors remains elusive. In this study, we demonstrate the structural basis for the binding of b...
Targeting Gli transcription activation by small molecule suppresses tumor growth.
Targeted inhibition of Hedgehog signaling at the cell membrane has been associated with anticancer activity in preclinical and early clinical studies. Hedgehog signaling involves activation of Gli transcription factors that can also be induced by alternative pathways. In this study, we identified an interaction between Gli proteins and a transcription coactivator TBP-associated factor 9 (TAF9), and validated its functional relevance in regulating Gli transactivation. We also describe a novel, synthetic smal...
The pleiotrophin-ALK axis is required for tumorigenicity of glioblastoma stem cells.
Increasing evidence suggests that brain tumors arise from the transformation of neural stem/precursor/progenitor cells. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma. Here we show that anaplastic lymphoma kinase (ALK) and its ligand pleiotrophin are required for the self-renewal and tumorigenicity of glioblastoma stem cells (GSCs). Furthermore, we demonstrate that pleiotrophin is transactivated directly by SOX2, a transcription factor essential for the ma...
The proto-oncogene BMI1 and its product, Bmi1, is overexpressed in various types of tumors, particularly in aggressive tumors and tumors resistant to conventional chemotherapy. BMI1/Bmi1 is also crucially involved in cancer-initiating cell maintenance, and is recurrently upregulated in mantle cell lymphoma (MCL), especially aggressive variants. Recently, side population (SP) cells were shown to exhibit tumor-initiating characteristics in various types of tumors. In this study, we show that recurrent MCL cas...
Control of gp130 expression by the mitogen-activated protein kinase ERK2.
Interleukin (IL)-6-type cytokines such as IL-6, oncostatin M (OSM) and leukaemia inhibitory factor (LIF) signal through receptor complexes that are critically dependent on gp130. The latter is the common signal-transducing molecule that couples these cytokines to their downstream effectors, Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). IL-6-type cytokine signalling additionally involves the recruitment and activation of extracellular signal-regulated kinase (ERK) 1 and...
DNA methylation determines nucleosome occupancy in the 5'-CpG islands of tumor suppressor genes.
Promoter CpG island hypermethylation of tumor suppressor genes is an epigenetic hallmark of human cancer commonly associated with nucleosome occupancy and the transcriptional silencing of the neighboring gene. Nucleosomes can determine the underlying DNA methylation status. Herein, we show that the opposite is also true: DNA methylation can determine nucleosome positioning. Using a cancer model and digital nucleosome positioning techniques, we demonstrate that the induction of DNA hypomethylation events by...
Multiple clinical studies have correlated gene expression with survival outcome in cancer on a genome-wide scale. However, in many cases, no obvious correlation between expression of well-known tumour-related genes (that is, p53, p73 and p21) and survival rates of patients has been observed. This can be mainly explained by the complex molecular mechanisms involved in cancer, which mask the clinical relevance of a gene with multiple functions if only gene expression status is considered. As we demonstrate he...
Profilin1 (Pfn1), a ubiquitously expressed actin-binding protein, has an indispensable role in migration and proliferation of normal cells. Seemingly contrary to its essential cellular functions, Pfn1's expression is downregulated in breast cancer, the significance of which is unclear. In this study, expression profiling of Pfn1 in human breast cancer specimens correlates lower Pfn1 expression levels with propensity to metastasize. Xenograft experiments further establish a causal relationship between loss o...
ANGPTL4 is a secreted tumor suppressor that inhibits angiogenesis.
Tumor suppressors with extracellular function are likely to have advantages as targets for cancer therapy, but few are known. Here, we focused on angiopoietin-like 4 (ANGPTL4), which is a secreted glycoprotein involved in lipoprotein metabolism and angiogenesis, is methylation-silenced in human cancers, but has unclear roles in cancer development and progression. We found a deletion mutation in its coiled-coil domain at its N-terminal in human gastric cancers, in addition to hypermethylation of the ANGPTL4...
SATB1 collaborates with loss of p16 in cellular transformation.
Tumor progression is associated with invasiveness and metastatic potential. The special AT-rich binding protein 1 (SATB1) has been identified as a key factor in the progression of breast cancer cells to a malignant phenotype and is associated with progression of human tumors. In normal development, SATB1 coordinates gene expression of progenitor cells by functioning as a genome organizer. In contrast to progenitor and tumor cells, SATB1 expression in nontransformed cells is not compatible with proliferation...
Simultaneous inhibition of the two major constitutive protein quality control (PQC) pathways, that is, the ubiquitin-proteasome system (UPS) and the aggresome-autophagy system, has been suggested as a promising strategy to trigger cell death in cancer cells. However, we observed that one third of rhabdomyosarcoma (RMS) cells survives parallel inhibition of the UPS by Bortezomib and the aggresome-autophagy pathway by the cytoplasmic histone deacetylase 6 inhibitor ST80, and is able to regrow upon drug remova...
The interactions between cancer cells and their microenvironment are crucial for malignant progression, as they modulate invasion-related activities. Tumor-associated macrophages are generally considered allies in the process of tumor progression in several types of cancer, although their role on gastric and colorectal carcinomas is still poorly understood. In this report, we studied the influence of primary human macrophages on gastric and colorectal cancer cells, considering invasion, motility/migration,...
Heparanase promotes lymphangiogenesis and tumor invasion in pancreatic neuroendocrine tumors.
Heparan sulfate proteoglycans are an important and abundant component of the extracellular matrix, which undergo substantial remodeling throughout tumorigenesis via the enzymatic activity of heparanase. Heparanase has been shown to be upregulated in many human cancers; however, its specific functions in human pancreatic neuroendocrine tumors (PanNETs) and spontaneous mouse models of cancer have not been evaluated. Here, we investigated the role of heparanase in PanNETs using patient samples and the RIP1-Tag...
Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability.
Changes in cell adhesion and polarity are closely associated with epithelial cell transformation and metastatic capacity. The tumor suppressor protein ASPP (Apoptosis-Stimulating Proteins of p53) 2 has been implicated in control of cell adhesion and polarity through its effect on the PAR complex. Here we demonstrate that under hypoxic conditions, the ubiquitin ligase Siah (seven in absentia homolog)2 controls ASPP2 availability, with concomitant effect on epithelial cell polarity. LC-MS/MS analysis identifi...
Gliomas represent the most frequent form of primary brain tumors in adults, the prognosis of which remains extremely poor. Inactivating mutations on the tumor suppressor TP53 were proposed as a key etiological trigger of glioma development. p53 has been recently identified as a transcriptional target of parkin. Interestingly, somatic mutations on parkin have also been linked to glioma genesis. We examined the possibility that a disruption of a functional interaction between p53 and parkin could contribute t...
It has been suggested that clec14a may be involved in tumor angiogenesis. However, a molecular mechanism has not been clearly identified. In this study, we show for the first time that C-type lectin-like domain (CTLD) of clec14a may be important for regulating cell migration and filopodia formation. Using phage display technology, recombinant human antibodies specific to the CTLDs of human and mouse clec14a (clec14a-CTLD (immunoglobulin G) IgG) were selected. Functional assays using the antibodies showed th...
Drosophila actin-Capping Protein limits JNK activation by the Src proto-oncogene.
The Src family kinases c-Src, and its downstream effectors, the Rho family of small GTPases RhoA and Jun N-terminal kinase (JNK) have a significant role in tumorigenesis. In this report, using the Drosophila wing disc epithelium as a model system, we demonstrate that the actin-Capping Protein (CP) αβ heterodimer, which regulates actin filament (F-actin) polymerization, limits Src-induced apoptosis or tissue overgrowth by restricting JNK activation. We show that overexpressing Src64B drives JNK-independent...
Translation factors and ribosomal proteins control tumor onset and progression: how?
Gene expression is shaped by translational control. The modalities and the extent by which translation factors modify gene expression have revealed therapeutic scenarios. For instance, eukaryotic initiation factor (eIF)4E activity is controlled by the signaling cascade of growth factors, and drives tumorigenesis by favoring the translation of specific mRNAs. Highly specific drugs target the activity of eIF4E. Indeed, the antitumor action of mTOR complex 1 (mTORc1) blockers like rapamycin relies on their cap...
Signaling through cyclin D-dependent kinases.
Research over the past quarter century has identified cyclin D-dependent kinases, CDK4 and CDK6, as the major oncogenic drivers among members of the CDK superfamily. CDK4/6 are rendered hyperactive in the majority of human cancers through a multitude of genomic alterations. Sustained activation of these protein kinases provides cancer cells with the power to enter the cell cycle continuously by triggering G1-S-phase transitions and dramatically shortening the duration of the G1 phase. It has also become cle...
CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity.
CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions. In osteosarcoma, CD99 is expressed at low levels and functions as a tumour suppressor. The full-length protein (CD99wt) and the short-form harbouring a deletion in the intracytoplasmic domain (CD99sh) have been associated with distinct functional outcomes with...
p16(INK4A) Represses the paracrine tumor-promoting effects of breast stromal fibroblasts.
Inhibitor of growth 4 induces NFκB/p65 ubiquitin-dependent degradation.
As a tumor suppressor protein, the inhibitor of growth 4 (ING4) has an important role in many cellular processes including cell cycle progression, proliferation, apoptosis, DNA damage response, tumor angiogenesis and contact inhibition. Here, we report that ING4 functions as an E3 ubiquitin ligase to induce nuclear factor-κB (NFκB)/p65 degradation. The plant homeodomain finger of ING4 interacted with p65 to undergo robust ubiquitination and degradation. ING4 bound to p65 and delivered the Lys-48-linked po...
Substrate-specific degradation is a key feature of the ubiquitin proteasome system. Substrate specificity is typically directed by the E3 or ubiquitin ligase; such specificity can be conferred either by ligase modification or expression or conversely via modification of substrates that permit their recognition by a specific E3 ligase. The most well-known example of such complexes are the Cullin-RING ligases (CRLs). CRLs are composed of one of seven cullin-family scaffold proteins; the CRL serves as a scaffo...
