Abstract:
:Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study, we investigated the role and therapeutic potential of CDK7 in regulating the angiogenic activity of endothelial cells and human renal cell carcinoma (RCC). Our results revealed that vascular endothelial growth factor (VEGF), a critical activator of angiogenesis, upregulated the expression of CDK7 and RNAPII, and the phosphorylation of RNAPII at serine 5 and 7 in human umbilical vein endothelial cells (HUVECs), indicating the transcriptional activity of CDK7 may be involved in VEGF-activated angiogenic activity of endothelium. Furthermore, through suppressing CDK7 activity, THZ1 suppressed VEGF-activated proliferation and migration, as well as enhanced apoptosis of HUVECs. Moreover, THZ1 inhibited VEGF-activated capillary tube formation and CDK7 knockdown consistently diminished tube formation in HUVECs. Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts. Our results demonstrated that CDK7-mediated transcription was involved in the angiogenic activity of endothelium and human RCC. THZ1 suppressed VEGF-mediated VEGFR2 downstream activation of angiogenesis, providing a new perspective for antitumor therapy in RCC patients.
journal_name
Cellsjournal_title
Cellsauthors
Shi CS,Kuo KL,Chen MS,Chow PM,Liu SH,Chang YW,Lin WC,Liao SM,Hsu CH,Hsu FS,Chang HC,Huang KHdoi
10.3390/cells8111469subject
Has Abstractpub_date
2019-11-19 00:00:00issue
11issn
2073-4409pii
cells8111469journal_volume
8pub_type
杂志文章相关文献
Cells文献大全abstract::Respiratory syncytial virus (RSV) infection affects the lives of neonates throughout the globe, causing a high rate of mortality upon hospital admission. Yet, therapeutic options to deal with this pulmonary pathogen are currently limited. Helminth therapy has been well received for its immunomodulatory role in hosts, ...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9051314
更新日期:2020-05-25 00:00:00
abstract::Hepatitis E virus (HEV) infection is one of the most common causes of acute hepatitis in the world. HEV is an enterically transmitted positive-strand RNA virus found as a non-enveloped particle in bile as well as stool and as a quasi-enveloped particle in blood. Current understanding of the molecular mechanisms and ho...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9051294
更新日期:2020-05-22 00:00:00
abstract::There is growing evidence that mesenchymal stem cell (MSC)-based immunosuppression was mainly attributed to the effects of MSC-derived extracellular vesicles (MSC-EVs). MSC-EVs are enriched with MSC-sourced bioactive molecules (messenger RNA (mRNA), microRNAs (miRNAs), cytokines, chemokines, immunomodulatory factors) ...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8121605
更新日期:2019-12-11 00:00:00
abstract::Anti-inflammatory treatment of chronic inflammatory diseases often increases susceptibility to infectious diseases such as tuberculosis (TB). Since numerous chronic inflammatory and autoimmune diseases are mediated by interleukin (IL)-6-induced T helper (TH) 17 cells, a TH17-directed anti-inflammatory therapy may be p...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells10010009
更新日期:2020-12-22 00:00:00
abstract::Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes angiogenesis. It has been established that regulatory loops exist between angiogenic growth factors and distinct pro or anti-angiogenic miRNAs, but the nature and the roles of Ang-1-regulated miRNAs remain unclear. In this study, we assessed the role ...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9071602
更新日期:2020-07-02 00:00:00
abstract::Respiratory syncytial virus (RSV) is a key cause of severe respiratory infection in infants, immunosuppressed adults, and the elderly worldwide, but there is no licensed vaccine or effective, widely-available antiviral therapeutic. We recently reported staged redistribution of host cell mitochondria in RSV infected ce...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8111417
更新日期:2019-11-11 00:00:00
abstract::Breast cancer-related mortality remains high worldwide, despite tremendous advances in diagnostics and therapeutics; hence, the quest for better strategies for disease management, as well as the identification of modifiable risk factors, continues. With recent leaps in genomic technologies, microbiota have emerged as ...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9051091
更新日期:2020-04-28 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::Despite major advances in the last 10 years, whether in terms of prevention or treatment, the 5 year survival rate remains relatively low for a large number of cancers. These therapeutic failures can be the consequence of several factors associated with the cellular modifications or with the host by itself, especially...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9020362
更新日期:2020-02-04 00:00:00
abstract::The role of kinases in the regulation of cell cycle transitions is very well established, however, over the past decade, studies have identified the ever-growing importance of phosphatases in these processes. It is well-known that an intact or otherwise non-deformed nuclear envelope (NE) is essential for maintaining h...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8070687
更新日期:2019-07-07 00:00:00
abstract::Feline coronavirus is a highly contagious virus potentially resulting in feline infectious peritonitis (FIP), while the pathogenesis of FIP remains not well understood, particularly in the events leading to the disease. A predominant theory is that the pathogenic FIPV arises from a mutation, so that it could replicate...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9061431
更新日期:2020-06-09 00:00:00
abstract::An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group ...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9010113
更新日期:2020-01-02 00:00:00
abstract::CCN1 and CCN2 are members of the CCN family and play essential roles in the regulation of multiple female reproductive functions, including ovulation. Cyclooxygenase-2 (COX2) is a critical mediator of ovulation and can be induced by sphingosine-1-phosphate (S1P) through the S1P1/3-mediated Yes-associated protein (YAP)...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8111445
更新日期:2019-11-15 00:00:00
abstract::Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer-related death and is the most common type of liver cancer. Due to the current paucity of drugs for HCC therapy there is a pressing need to develop new therapeutic concepts. In recent years, the role of Serum Response Factor (SRF) and its coactivator...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9122540
更新日期:2020-11-25 00:00:00
abstract::In this study we report the functional comparison of T cell receptor (TCR)-engineered major histocompatibility complex (MHC) class I-restricted CD4+ versus CD8+ T cells targeting a peptide from six transmembrane epithelial antigen of the prostate 1 (STEAP1) in the context of HLA-A*02:01. STEAP1 is a tumor-associated a...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9071581
更新日期:2020-06-29 00:00:00
abstract::Telomere dysfunction has been strongly implicated in the initiation of genomic instability and is suspected to be an early event in the carcinogenesis of human solid tumors. Recent findings have established the presence of telomere fusions in human breast and prostate malignancies; however, the onset of this genomic i...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8050414
更新日期:2019-05-04 00:00:00
abstract::Many receptors for neurotransmitters, such as dopamine, norepinephrine, acetylcholine, and neuropeptides, belong to the superfamily of G protein-coupled receptors (GPCRs). A general model posits that GPCRs undergo two-step homologous desensitization: the active receptor is phosphorylated by kinases of the G protein-co...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells10010052
更新日期:2020-12-31 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::L-Ascorbate (Asc) plays important roles in cell growth and plant development, and its de novo biosynthesis was catalyzed by the first rate-limiting enzyme VTC1. However, the function and regulatory mechanism of VTC1 involved in cell development is obscure in Gossypium hirsutum. Herein, the Asc content and AsA/DHA rati...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8091039
更新日期:2019-09-05 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::Small guanosine triphosphatases (GTPases) gathered in the Rat sarcoma (Ras) superfamily represent a large family of proteins involved in several key cellular mechanisms. Within the Ras superfamily, the Ras homolog (Rho) family is specialized in the regulation of actin cytoskeleton-based mechanisms. These proteins swit...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8040351
更新日期:2019-04-12 00:00:00
abstract::Mesenchymal stromal cells (MSCs) from various sources exhibit different potential for stemness and therapeutic abilities. Recently, we reported a unique MSCs from human palatine tonsil (TMSCs) and their superior proliferation capacity compared to MSCs from other sources. However, unique characteristics of each MSC are...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9030636
更新日期:2020-03-06 00:00:00
abstract::Obesity is a well-known risk factor for insulin resistance syndrome (IRS). Nevertheless, limited data are available regarding the effects of physical activity (PA) intensity on the ability to modulate IRS. The study aim was to investigate the beneficial effects of the longer duration of light PA vs. a single bout of t...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells9051189
更新日期:2020-05-11 00:00:00
abstract::Exosomes are endosome-derived nanovesicles produced by healthy as well as diseased cells. Their proteic, lipidic and nucleic acid composition is related to the cell of origin, and by vehiculating bioactive molecules they are involved in cell-to-cell signaling, both in healthy and pathologic conditions. Being nano-size...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9122569
更新日期:2020-12-01 00:00:00
abstract::Vector transmission of plant viruses is basically of two types that depend on the virus helper component proteins or the capsid proteins. A number of plant viruses belonging to disparate groups have developed unusual capsid proteins providing for interactions with the vector. Thus, cauliflower mosaic virus, a plant pa...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells10010090
更新日期:2021-01-07 00:00:00
abstract::Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. L...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells8121633
更新日期:2019-12-13 00:00:00
abstract::Extracellular vesicles (EVs) are involved in intercellular communication during carcinogenesis, and cancer cells are able to secrete EVs, in particular exosomes containing molecules, that can be transferred to recipient cells to induce pathological processes and significant modifications, as metastasis, increase of pr...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8080777
更新日期:2019-07-25 00:00:00
abstract::This study was aimed to investigate the role of SHP2 (Src-homology-2-containing phosphotyrosine phosphatase) in intricate signaling networks invoked by bovine oocyte to achieve maturation and blastocyst development. PTPN11 (Protein Tyrosine Phosphatase, non-receptor type 11) encoding protein SHP2, a positive transduce...
journal_title:Cells
pub_type: 杂志文章
doi:10.3390/cells8101272
更新日期:2019-10-18 00:00:00
abstract::During tumor progression, hypoxia, nutrient deprivation or changes in the extracellular environment (i.e., induced by anti-cancer drugs) elicit adaptive responses in cancer cells. Cellular plasticity increases the chance that tumor cells may survive in a challenging microenvironment, acquire new mechanisms of resistan...
journal_title:Cells
pub_type: 杂志文章,评审
doi:10.3390/cells9010034
更新日期:2019-12-21 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