Abstract：
:Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2-) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Ding L,Cao J,Lin W,Chen H,Xiong X,Ao H,Yu M,Lin J,Cui Qdoi
10.3390/ijms21061960subject
Has Abstractpub_date
2020-03-13 00:00:00issue
6issn
1422-0067pii
ijms21061960journal_volume
21pub_type
杂志文章,评审abstract：:Phosphodiesterases (PDEs) are essential enzymes for the regulation of pathways mediated by cyclic adenosine monophosphate (cAMP). Secondary plant compounds like anthocyanins (ACs) can inhibit PDE activity and, consequently, may be beneficial for lipid metabolism. This study investigated 18 AC-rich juice extracts and p...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21186934
更新日期：2020-09-21 00:00:00
abstract：:Metal tolerance proteins (MTPs) are plant divalent cation transporters that play important roles in plant metal tolerance and homeostasis. Poplar is an ideal candidate for the phytoremediation of heavy metals because of its numerous beneficial attributes. However, the definitive phylogeny and heavy metal transport mec...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21051680
更新日期：2020-02-29 00:00:00
abstract：:Neuropeptides such as vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are present in nerve fibers of bone tissues and have been suggested to potentially regulate bone remodeling. Oscillatory fluid flow (OFF)-induced shear stress is a potent signal in mechanotransduction that is capable o...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms15045874
更新日期：2014-04-08 00:00:00
abstract：:Glutathione synthetases catalyze the ATP-dependent synthesis of glutathione from l-γ-glutamyl- l-cysteine and glycine. Although these enzymes have been sequenced and characterized from a variety of biological sources, their exact catalytic mechanism is not fully understood and nothing is known about their adaptation a...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms12096312
更新日期：2011-01-01 00:00:00
abstract：:Chronic inflammation in adipose tissue may contribute to depot-specific adipose tissue expansion, leading to obesity and insulin resistance. Dietary supplementation with quercetin or botanical extracts containing quercetin attenuates high fat diet (HFD)-induced obesity and insulin resistance and decreases inflammation...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19030895
更新日期：2018-03-17 00:00:00
abstract：:The endoplasmic reticulum (ER) is the principal organelle responsible for correct protein folding, a step in protein synthesis that is critical for the functional conformation of proteins. ER stress is a primary feature of secretory cells and is involved in the pathogenesis of numerous human diseases, such as certain ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms17020192
更新日期：2016-02-01 00:00:00
abstract：:Patients harbouring mutations in genes encoding C-type natriuretic peptide (CNP; NPPC) or its receptor guanylyl cyclase B (GC-B, NPR2) suffer from severe growth phenotypes; loss-of-function mutations cause achondroplasia, whereas gain-of-function mutations cause skeletal overgrowth. Although most of the effects of CNP...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms22031076
更新日期：2021-01-22 00:00:00
abstract：:Plants are able to synthesize all essential metabolites from minerals, water, and light to complete their life cycle. This plasticity comes at a high energy cost, and therefore, plants need to tightly allocate resources in order to control their economy. Being sessile, plants can only adapt to fluctuating environmenta...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21082771
更新日期：2020-04-16 00:00:00
abstract：:Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL), an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investig...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18102025
更新日期：2017-09-21 00:00:00
abstract：:ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developme...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21207790
更新日期：2020-10-21 00:00:00
abstract：:Of the multiple sources of reactive oxygen species (ROS) in the blood vessel, NADPH oxidases are the primary source. Whereas several studies have implicated NADPH oxidases in the initiation of atherosclerosis, their roles in disease progression are incompletely understood. Our objective was to determine the potential ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms140817017
更新日期：2013-08-19 00:00:00
abstract：:Realizing the full potential of magnetic nanoparticles (MNPs) in nanomedicine requires the optimization of their physical and chemical properties. Elucidation of the effects of these properties on clinical diagnostic or therapeutic properties, however, requires the synthesis or purification of homogenous samples, whic...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms160820001
更新日期：2015-08-21 00:00:00
abstract：:Maintaining a robust epithelial barrier requires the accumulation of tight junction proteins, LSR/angulin-1 and tricellulin, at the tricellular contacts. Alterations in the localization of these proteins temporarily cause epithelial barrier dysfunction, which is closely associated with not only physiological different...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms20143555
更新日期：2019-07-20 00:00:00
abstract：:Nerve growth factor (NGF) promotes the survival and differentiation of neurons. NGF is initially synthesized as a precursor, proNGF, which is the predominant form in the central nervous system. NGF and proNGF bind to TrkA/p75NTR to mediate cell survival and to sortilin/p75NTR to promote apoptosis. The ratio of TrkA to...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18030599
更新日期：2017-03-09 00:00:00
abstract：:The glycoprotein P-selectin belongs to the selectin family of cell adhesion molecules. In this study, we cloned the full-length cDNA of P-selectin from zebrafish (Danio rerio) by the method of rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR). Zebrafish P-selectin cDNA is 2,800 bp and encodes a put...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms11114618
更新日期：2010-11-17 00:00:00
abstract：:In recent years it has become apparent that aminoacyl-tRNAs are not only crucial components involved in protein biosynthesis, but are also used as substrates and amino acid donors in a variety of other important cellular processes, ranging from bacterial cell wall biosynthesis and lipid modification to protein turnove...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms150814610
更新日期：2014-08-21 00:00:00
abstract：:Chlorogenic acid (CGA) decreases colon cancer-cell proliferation but the combined anti-cancer effects of CGA with its major colonic microbial metabolites, caffeic acid (CA), 3-phenylpropionic acid (3-PPA) and benzoic acid (BA), needs elucidation as they occur together in colonic digesta. Caco-2 cancer cells were treat...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19030723
更新日期：2018-03-03 00:00:00
abstract：:Understanding the role of substituents is of great importance for the preparation of novel phenolic compounds with enhanced antioxidative properties. In this work, the antioxidative activity of isoflavonoid derivatives with different substituents placed at the C2 position was determined by density functional theory (D...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20020397
更新日期：2019-01-18 00:00:00
abstract：:Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting ske...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms22010255
更新日期：2020-12-29 00:00:00
abstract：:In this study, the effect of the acetone extract of Arctotis arctotoides (L.f.) O. Hoffm. (Asteraceae) on the growth and ultrastructure of some opportunistic fungi associated with HIV/AIDS was analyzed by means of scanning electron microscope (SEM). Remarkable morphological alterations in the fungal mycelia which were...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms12129226
更新日期：2011-01-01 00:00:00
abstract：:Cystic fibrosis is an inherited multi-organ disorder caused by mutations in the CFTR gene. Patients with this disease exhibit characteristic abnormalities in the levels of unsaturated fatty acids in blood and tissue. Recent studies have uncovered an underlying biochemical mechanism for some of these changes, namely in...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms150916083
更新日期：2014-09-11 00:00:00
abstract：BACKGROUND:P1G10 is a cysteine proteolytic fraction from Vasconcellea cundinamarcensis latex, obtained by chromatographic separation on Sephadex-G10 and ultrafiltration. This fraction enhances healing in different models of skin lesions, and displays a protective/healing effect against gastric ulcers, where it was sugg...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20184373
更新日期：2019-09-06 00:00:00
abstract：:Abiotic stresses are major constraints limiting crop growth and production. Heat shock factors (Hsfs) play significant roles in mediating plant resistance to various environmental stresses, including heat, drought and salinity. In this study, we explored the biological functions and underlying mechanisms of wheat TaHs...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21093121
更新日期：2020-04-28 00:00:00
abstract：:Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer's disease and their gene expression (amylo...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21134599
更新日期：2020-06-28 00:00:00
abstract：:The discovery of siRNAs as the mediators of RNA interference has led to an increasing interest in their therapeutic applications. Chemical modifications are introduced into siRNAs to optimize the potency, the stability and the pharmacokinetic properties in vivo. Here, we synthesize and test the effects of RNA-3'-PNA c...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms9030299
更新日期：2008-03-01 00:00:00
abstract：:Facioscapulohumeral muscular dystrophy (FSHD) is a disabling inherited muscular disorder characterized by asymmetric, progressive muscle weakness and degeneration. Patients display widely variable disease onset and severity, and sometimes present with extra-muscular symptoms. There is a consensus that FSHD is caused b...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21030729
更新日期：2020-01-22 00:00:00
abstract：:The Wnt signalling pathway is a central communication cascade between cells to orchestrate polarity and fate during development and adult tissue homeostasis in various organisms. This pathway can be regulated by different signalling molecules in several steps. One of the coordinators in this pathway is Nemo-like kinas...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21239203
更新日期：2020-12-02 00:00:00
abstract：:Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17050787
更新日期：2016-05-21 00:00:00
abstract：:Phenolic compounds are responsible of the nutritional and sensory quality of extra-virgin olive oil (EVOO). The composition of phenolic compounds in EVOO is related to the initial content of phenolic compounds in the olive-fruit tissues and the activity of enzymes acting on these compounds during the industrial proces...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms17030337
更新日期：2016-03-04 00:00:00
abstract：:The identification of biomarkers for early diagnosis of Parkinson's disease (PD) is of pivotal importance for improving approaches for clinical intervention. The use of translatable animal models of pre-motor PD therefore offers optimal opportunities for novel biomarker discovery in vivo. Peptidylarginine deiminases (...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21082743
更新日期：2020-04-15 00:00:00
