Search results for "TRANSFORMATION"
showing 10 items of 1634 documents
Kinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis.
2017
The mechanisms that regulate cell death and inflammation play an important role in liver disease and cancer. Receptor-interacting protein kinase 1 (RIPK1) induces apoptosis and necroptosis via kinase-dependent mechanisms and exhibits kinase-independent prosurvival and proinflammatory functions. Here, we have used genetic mouse models to study the role of RIPK1 in liver homeostasis, injury, and cancer. While ablating either RIPK1 or RelA in liver parenchymal cells (LPCs) did not cause spontaneous liver pathology, mice with combined deficiency of RIPK1 and RelA in LPCs showed increased hepatocyte apoptosis and developed spontaneous chronic liver disease and cancer that were independent of TNF…
Mechanism and biological role of Dnmt2 in Nucleic Acid Methylation
2016
ABSTRACT A group of homologous nucleic acid modification enzymes called Dnmt2, Trdmt1, Pmt1, DnmA, and Ehmet in different model organisms catalyze the transfer of a methyl group from the cofactor S-adenosyl-methionine (SAM) to the carbon-5 of cytosine residues. Originally considered as DNA MTases, these enzymes were shown to be tRNA methyltransferases about a decade ago. Between the presumed involvement in DNA modification-related epigenetics, and the recent foray into the RNA modification field, significant progress has characterized Dnmt2-related research. Here, we review this progress in its diverse facets including molecular evolution, structural biology, biochemistry, chemical biology,…
Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness
2018
The loss of epithelial cell polarity plays an important role in the development and progression of liver cancer. However, the specific molecular mechanisms supporting tumor initiation and progression are poorly understood. In this study, transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the baso-lateral cell polarity complex protein Scribble (Scrib) correlated with poor prognosis of HCC patients. In comparison to HCC cells stably expressing wildtype Scrib (ScribWT), mutated Scrib with enforced cytoplasmic enrichment (ScribP305L) induced AKT signaling…
Molecular chaperones in tumors of salivary glands.
2020
The salivary glands are key components of the mouth and play a central role in its physiology. Their importance may be appreciated considering their number, occurrence in pairs, and distribution in the mouth: two parotids, two submandibular, two sublingual, and many other small ones scattered throughout the mouth. They produce saliva, without which ingestion of non-liquid nutrients and speech would be practically impossible. Nevertheless, the physiology and pathology of salivary glands are poorly understood. For instance, tumors of salivary glands occur, and their incidence is on the rise, but their etiology and pathogenesis are virtually unknown, although some risk factors have been identi…
Human Intrinsic Factor Expression for Bioavailable Vitamin B12 Enrichment in Microalgae
2018
Dietary supplements and functional foods are becoming increasingly popular complements to regular diets. A recurring ingredient is the essential cofactor vitamin B12(B12). Microalgae are making their way into the dietary supplement and functional food market but do not produce B12, and their B12 content is very variable. In this study, the suitability of using the human B12-binding protein intrinsic factor (IF) to enrich bioavailable B12 using microalgae was tested. The IF protein was successfully expressed from the nuclear genome of the model microalga Chlamydomonas reinhardtii and the addition of an N-terminal ARS2 signal peptide resulted in efficient IF secretion to the medium. Co-abunda…
Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis
2018
Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium. E6 and E7 viral proteins are involved in the process of carcinogenesis. They interact with suppressors of oncogenesis, including p53 and Rb proteins. Th…
The wasted chewing gum bacteriome
2020
Here we show the bacteriome of wasted chewing gums from five different countries and the microbial successions on wasted gums during three months of outdoors exposure. In addition, a collection of bacterial strains from wasted gums was set, and the biodegradation capability of different gum ingredients by the isolates was tested. Our results reveal that the oral microbiota present in gums after being chewed, characterised by the presence of species such as Streptococcus spp. or Corynebacterium spp., evolves in a few weeks to an environmental bacteriome characterised by the presence of Acinetobacter spp., Sphingomonas spp. and Pseudomonas spp. Wasted chewing gums collected worldwide contain …
Et tu, Brute? Not Even Intracellular Mutualistic Symbionts Escape Horizontal Gene Transfer
2017
Many insect species maintain mutualistic relationships with endosymbiotic bacteria. In contrast to their free-living relatives, horizontal gene transfer (HGT) has traditionally been considered rare in long-term endosymbionts. Nevertheless, meta-omics exploration of certain symbiotic models has unveiled an increasing number of bacteria-bacteria and bacteria-host genetic transfers. The abundance and function of transferred loci suggest that HGT might play a major role in the evolution of the corresponding consortia, enhancing their adaptive value or buffering detrimental effects derived from the reductive evolution of endosymbionts' genomes. Here, we comprehensively review the HGT cases recor…
Characterization of zolbetuximab in pancreatic cancer models
2018
ABSTRACT In healthy tissue, the tight junction protein Claudin 18.2 (CLDN18.2) is present only in the gastric mucosa. Upon malignant transformation of gastric epithelial tissue, perturbations in cell polarity lead to cell surface exposure of CLDN18.2 epitopes. Moreover, CLDN18.2 is aberrantly expressed in malignancies of several other organs, such as pancreatic cancer (PC). A monoclonal antibody, zolbetuximab (formerly known as IMAB362), has been generated against CLDN18.2. In a phase 2 clinical trial (FAST: NCT01630083), zolbetuximab in conjunction with chemotherapy prolonged overall and progression-free survival over chemotherapy alone and improved quality of life. In this study, the mech…
ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells
2020
Lipid Droplets (LDs) are emerging as crucial players in colon cancer development and maintenance. Their expression has been associated with high tumorigenicity in Cancer Stem Cells (CSCs), so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells (CR-CSCs). They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory molecules. There is growing evidence that a possible connection between metabolic alterations and malignant transformation exists, although the effects of nutrients, primarily glucose, on the CSC behavior are still mostly unexplored. Glucose is an essential fuel for cancer cells, an…