Abstract：
:Cystic Fibrosis (CF) is caused by >2000 mutations in the CF transmembrane conductance regulator (CFTR) gene, but one mutation-F508del-occurs in ~80% of patients worldwide. Besides its main function as an anion channel, the CFTR protein has been implicated in epithelial differentiation, tissue regeneration, and, when dysfunctional, cancer. However, the mechanisms that regulate such relationships are not fully elucidated. Krüppel-like factors (KLFs) are a family of transcription factors (TFs) playing central roles in development, stem cell differentiation, and proliferation. Herein, we hypothesized that these TFs might have an impact on CFTR expression and function, being its missing link to differentiation. Our results indicate that KLF4 (but not KLF2 nor KLF5) is upregulated in CF vs. non-CF cells and that it negatively regulates wt-CFTR expression and function. Of note, F508del-CFTR expressing cells are insensitive to KLF4 modulation. Next, we investigated which KLF4-related pathways have an effect on CFTR. Our data also show that KLF4 modulates wt-CFTR (but not F508del-CFTR) via both the serine/threonine kinase AKT1 (AKT) and glycogen synthase kinase 3 beta (GSK3β) signaling. While AKT acts positively, GSK3β is a negative regulator of CFTR. This crosstalk between wt-CFTR and KLF4 via AKT/ GSK3β signaling, which is disrupted in CF, constitutes a novel mechanism linking CFTR to the epithelial differentiation.
journal_name
Cellsjournal_title
Cellsauthors
Sousa L,Pankonien I,Clarke LA,Silva I,Kunzelmann K,Amaral MDdoi
10.3390/cells9071607subject
Has Abstractpub_date
2020-07-02 00:00:00issue
7issn
2073-4409pii
cells9071607journal_volume
9pub_type
杂志文章相关文献
Cells文献大全abstract：:Disseminated metastatic cancer cells represent one of the most relevant causes of disease relapse and associated death for cancer patients, and a therapeutic target of the highest priority. Still, our understanding of how disseminated cancer cells survive in the foreign metastatic environment, and eventually cause met...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9010250
更新日期：2020-01-19 00:00:00
abstract：:Calcific aortic valve stenosis (CAVS) is a common age-related disease characterized by active calcification of the leaflets of the aortic valve. How innate immune cells are involved in disease pathogenesis is not clear. In this study we investigate the role of the pattern recognition receptor Toll-like receptor 7 (TLR...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9071710
更新日期：2020-07-16 00:00:00
abstract：:The family of heterochromatin protein 1 (HP1) isoforms is essential for chromatin packaging, regulation of gene expression, and repair of damaged DNA. Here we document that γ-radiation reduced the number of HP1α-positive foci, but not HP1β and HP1γ foci, located in the vicinity of the fibrillarin-positive region of th...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8091097
更新日期：2019-09-17 00:00:00
abstract：:Large tumor-derived Extracellular Vesicles (tdEVs) detected in blood of metastatic prostate, breast, colorectal, and non-small cell lung cancer patients after enrichment for Epithelial Cell Adhesion Molecule (EpCAM) expression and labeling with 4',6-diamidino-2-phenylindole (DAPI), phycoerythrin-conjugated antibodies ...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8080937
更新日期：2019-08-20 00:00:00
abstract：:Cell division cycle 42 (CDC42), a small Rho GTPase, plays a critical role in many cellular processes, including cell proliferation and survival. CDC42 interacts with the CRIB (Cdc42- and Rac-interactive binding) domain of CDC42SE1, a small effector protein of 9 kDa. We found that the expression of CDC42SE1 was reduced...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8020117
更新日期：2019-02-02 00:00:00
abstract：:Epithelial-mesenchymal transition (EMT) is strongly correlated with tumor metastasis and contains several protein markers, such as E-cadherin. Carbonic anhydrase III (CA III) exhibits low carbon dioxide hydratase activity in cancer. However, the detailed mechanisms of CA III and their roles in oral cancer are still un...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9030704
更新日期：2020-03-13 00:00:00
abstract：:Cyclic AMP promotes EPAC1 and EPAC2 activation through direct binding to a specific cyclic nucleotide-binding domain (CNBD) within each protein, leading to activation of Rap GTPases, which control multiple cell responses, including cell proliferation, adhesion, morphology, exocytosis, and gene expression. As a result,...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8111425
更新日期：2019-11-12 00:00:00
abstract：:Over a decade ago, the formation of neutrophil extracellular traps (NETs) was described as a novel mechanism employed by neutrophils to tackle infections. Currently applied methods for NETs release quantification are often limited by the use of unspecific dyes and technical difficulties. Therefore, we aimed to develop...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9020508
更新日期：2020-02-24 00:00:00
abstract：:Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, ...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9061503
更新日期：2020-06-20 00:00:00
abstract：:Purine nucleotides are involved in a multitude of cellular processes, and the dysfunction of purine metabolism has drastic physiological and pathological consequences. Accordingly, several genetic disorders associated with defective purine metabolism have been reported. The etiology of these diseases is poorly underst...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8010067
更新日期：2019-01-17 00:00:00
abstract：:More than 50% of human cancers harbor TP53 mutations and increased expression of Mouse double minute 2 homolog(MDM2), which contribute to cancer progression and drug resistance. Renal cell carcinoma (RCC) has an unusually high incidence of wild-type p53, with a mutation rate of less than 4%. MDM2 is master regulator o...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9061475
更新日期：2020-06-16 00:00:00
abstract：:(1) Background: Hyperglycemia leads to several biochemical and physiological consequences, such as the generation of advanced glycation end products (AGEs) and reactive oxygen species (ROS), which are involved in the development of several human diseases. Intestinal cells are continuously exposed to pro-oxidants and l...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8121616
更新日期：2019-12-11 00:00:00
abstract：:Stroke is a leading cause of death and disability globally and is associated with a number of co-morbidities including sepsis and sickle cell disease (SCD). Despite thrombo-inflammation underlying these co-morbidities, its pathogenesis remains complicated and drug discovery programs aimed at reducing and resolving the...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9112473
更新日期：2020-11-13 00:00:00
abstract：:The MRE11-RAD50-NBS1 (MRN) protein complex is one of the primary vehicles for repairing DNA double strand breaks and maintaining the genomic stability within the cell. The role of the MRN complex to recognize and process DNA double-strand breaks as well as signal other damage response factors is critical for maintaini...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9071678
更新日期：2020-07-13 00:00:00
abstract：:Vinyl chloride (VC) is a noninfective occupational risk factor. It is found in industrial chemicals, volatile organic compounds, cigarette smoke ingredients, etc. It is a kind of toxic gas that causes many diseases. VC exposure causes an increased risk of liver fibrosis and can result in angiosarcoma of the liver. Pre...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8060601
更新日期：2019-06-17 00:00:00
abstract：:Tumor-infiltrating lymphocytes are known to be critical in controlling tumor progression. While the role of T lymphocytes has been extensively studied, the function of B cells in this context is still ill-defined. In this review, we propose to explore the role of B cells in tumor immunity. First of all we define their...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8050449
更新日期：2019-05-13 00:00:00
abstract：:The zygote is defined as a diploid cell resulting from the fusion of two haploid gametes. Union of haploid male and female pronuclei in many animals occurs through rearrangements of the microtubule cytoskeleton into a radial array of microtubules known as the sperm aster. The sperm aster nucleates from paternally-deri...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9020505
更新日期：2020-02-23 00:00:00
abstract：:Mutations in tubulin genes are responsible for a large spectrum of brain malformations secondary to abnormal neuronal migration, organization, differentiation and axon guidance and maintenance. Motor impairment, intellectual disability and epilepsy are the main clinical symptoms. In the present study 15 patients from ...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8070669
更新日期：2019-07-02 00:00:00
abstract：:HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Deri...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells10010192
更新日期：2021-01-19 00:00:00
abstract：:The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated sele...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9112416
更新日期：2020-11-04 00:00:00
abstract：:Canonical transient receptor potential (TRPC) channels are a family of polymodal cation channels with some degree of Ca2+ permeability. Although initially thought to be channels mediating store-operated Ca2+ influx, TRPC channels can be activated by stimulation of Gq-coupled G-protein coupled receptors, or by an incre...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells3020288
更新日期：2014-04-09 00:00:00
abstract：:Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate wheth...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells8101142
更新日期：2019-09-25 00:00:00
abstract：:: Cholangiocarcinoma (CCA) comprises a group of heterogeneous biliary cancers with dismal prognosis. The etiologies of most CCAs are unknown, but primary sclerosing cholangitis (PSC) is a risk factor. Non-invasive diagnosis of CCA is challenging and accurate biomarkers are lacking. We aimed to characterize the transcr...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9030721
更新日期：2020-03-14 00:00:00
abstract：:In eukaryotic cells, a spindle assembly checkpoint (SAC) ensures accurate chromosome segregation, by monitoring proper attachment of chromosomes to spindle microtubules and delaying mitotic progression if connections are erroneous or absent. The SAC is thought to be relaxed during early embryonic development. Here, we...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9051087
更新日期：2020-04-28 00:00:00
abstract：:Transient receptor potential classical or canonical 4 (TRPC4) and TRPC5 channels are members of the classical or canonical transient receptor potential (TRPC) channel family of non-selective cation channels. TRPC4 and TRPC5 channels are widely accepted as receptor-operated cation channels that are activated in a phosp...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells7110218
更新日期：2018-11-20 00:00:00
abstract：:Blood-derived microRNA signatures have emerged as powerful biomarkers for predicting and diagnosing cardiovascular disease, cancer, and metabolic disorders. Platelets and platelet-derived microvesicles are a major source of microRNAs. We have previously shown that the inappropriate anticoagulation and storage of blood...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9081915
更新日期：2020-08-18 00:00:00
abstract：:Pharmaco-therapeutic strategies of atrial fibrillation (AF) are moderately effective and do not prevent AF onset and progression. Therefore, there is an urgent need to develop novel therapies. Previous studies revealed heat shock protein (HSP)-inducing compounds to mitigate AF onset and progression. Such an HSP induci...
journal_title：Cells
pub_type： 杂志文章
doi：10.3390/cells9071729
更新日期：2020-07-20 00:00:00
abstract：:We developed tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R, a facultative anaerobe that is an auxotroph of leucine and arginine. The tumor-targeting efficacy of S. typhimurium A1-R was demonstrated in vivo and vitro using several malignant cell lines including melanoma, sarcoma, glioma, breast, pancreat...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells8060599
更新日期：2019-06-16 00:00:00
abstract：:The genomes of all organisms abound with various cis-regulatory elements, which control gene activity. Transcriptional enhancers are a key group of such elements in eukaryotes and are DNA regions that form physical contacts with gene promoters and precisely orchestrate gene expression programs. Here, we follow gradual...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9071675
更新日期：2020-07-12 00:00:00
abstract：:The Epithelial Cell Adhesion Molecule or EpCAM is a well-known marker highly expressed in carcinomas and showing a strong correlation with poor cancer prognosis. While its name relates to its proposed function as a cell adhesion molecule, EpCAM has been shown to have various signalling functions. In particular, it has...
journal_title：Cells
pub_type： 杂志文章,评审
doi：10.3390/cells9092128
更新日期：2020-09-19 00:00:00
