Abstract:
:Aims and Hypothesis: This study aims to investigate the mechanism involved in intracellular regulation of EGFR degradation induced by EGF. Methods: Phosphorylation of proteins related to EGFR signaling was examined by western blot analysis. Activation, connection between Rab35 and folliculin (FLCN) were assessed by pulldown, coimmunoprecipitation assays separately. The relationship between FLCN and cell growth was detected using gene overexpression and knock-down techniques. Results: Here, we demonstrate that interfering with FLCN, a tumor suppressor, reduces the rate of EGF-induced EGFR degradation, resulting in prolonged activation of downstream signaling. Rab35 is also involved in these processes. Moreover, C-terminal of FLCN binds to and activates Rab35. Of special interest is the observation that erlotinib, a selective EGFR inhibitor, not only obstructs the EGFR-mediated cellular signaling, but also abolishes EGF-stimulated EGFR degradation. Further results reveal that EGF facilitates the activation of Rab35, and FLCN modulates EGF-dependent Rab35 activation and cell growth. Conclusions: Taken together, our study proposes a negative-feedback regulation model in which FLCN mediates EGF-induced Rab35 activation, thereby increasing EGFR degradation and attenuating EGFR signaling.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Zheng J,Duan B,Sun S,Cui J,Du J,Zhang Ydoi
10.3389/fphar.2017.00688subject
Has Abstractpub_date
2017-09-26 00:00:00pages
688issn
1663-9812journal_volume
8pub_type
杂志文章abstract::Background: To assess the health-related quality of life (HRQoL) of oral anticoagulant therapy users, different types of instruments are available, either general or specific tools like Duke Anticoagulation Satisfaction Scale (DASS). These tools allow the clinician to adjust the treatment regimen to focus on increasin...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.587489
更新日期:2020-12-17 00:00:00
abstract::In spite of recent therapeutic advances, multiple myeloma (MM) remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs). MM-CSCs are equipped with the necessary tools that render them highly resistant to virtuall...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00610
更新日期:2017-09-08 00:00:00
abstract:BACKGROUND:Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00123
更新日期:2016-05-18 00:00:00
abstract::Neurofibrillary pathology contributes to neuronal dysfunction and correlates with the clinical progression of Alzheimer's disease (AD). Tau phosphorylation is mainly regulated by a balance of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) activities. Cornel iridoid glycoside (CIG) is a main com...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00682
更新日期:2018-06-26 00:00:00
abstract::Cataract is the leading reason of blindness worldwide and is defined by the presence of any lens opacities or loss of transparency. The most common symptoms of cataract are impaired vision, decreased contrast sensitivity, color disturbance, and glare. Oxidative stress is among the main mechanisms involved in the devel...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00466
更新日期:2019-06-13 00:00:00
abstract::Background: This study aimed to explore the intellectual landscape of the studies investigating the clinical application of enteral nutrition (EN) in patients with ventilator associated pneumonia (VAP), and to identify thematic development trends and research frontiers in this area. Methods: Scientometric research was...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00246
更新日期:2019-03-20 00:00:00
abstract::The objective of this study was to test the hypothesis that serotonin O-sulphate (5-HT-SO4) could be quantified in human plasma using modern liquid chromatography-mass spectrometry (LC-MS) method as well as develop and validate that method. First, a suitable LC-MS method for detection of 5-HT-SO4 in human plasma sampl...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2014.00062
更新日期:2014-04-08 00:00:00
abstract::Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2016.00487
更新日期:2016-12-20 00:00:00
abstract::Since the clinical use of digitalis as the first pharmacological therapy for atrial fibrillation (AF) 235 years ago in 1785, antiarrhythmic drug therapy has advanced considerably and become a cornerstone of AF clinical management. Yet, a preventive or curative panacea for sustained AF does not exist despite the rise o...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.581837
更新日期:2020-11-09 00:00:00
abstract::Low solubility, tissue accumulation, and toxicity are chief obstacles to developing triptolide derivatives, so a better understanding of the pharmacokinetics and toxicity of triptolide derivatives will help with these limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5-hydroxytriptolide (L...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00832
更新日期:2017-11-21 00:00:00
abstract::Several reports have shown that the periventricular region of the brain, including the paraventricular nucleus (PVN), is critical to sensing and responding to changes in plasma osmolality. Further studies also implicate the transient receptor potential ion channel, type V4 (TRPV4) channel in this homeostatic behavior....
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00083
更新日期:2015-04-23 00:00:00
abstract::Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.569651
更新日期:2020-10-19 00:00:00
abstract:Background:Dose requirements of vitamin K antagonists are associated with CYP2C9 and VKORC1, but, compared to warfarin, less data is available about phenprocoumon. Furthermore, the effects on dose stability and anticoagulation quality are still unclear. Methods:Aim was to scrutinize phenprocoumon dose requirements, do...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01620
更新日期:2020-01-28 00:00:00
abstract::P-Glycoprotein (P-gp, Abcb1) plays a crucial role in drug disposition and functions by hydrolyzing ATP. However, little is known about the regulatory elements governing the transcription of the porcine Abcb1 gene. In this study, the transcription start site of the pig Abcb1 gene was identified by 5'-RACE. A 1.9-kb fra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00373
更新日期:2018-05-04 00:00:00
abstract::Alzheimer's disease (AD) is the most widespread form of dementia, affecting about 45 million people worldwide. Although the β-amyloid peptide (Aβ) remains the most acknowledged culprit of AD, the multiple failures of Aβ-centric therapies call for alternative therapeutic approaches. Conceivably, the complexity of the A...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00738
更新日期:2019-07-03 00:00:00
abstract::High-throughput techniques allow for massive screening of drug combinations. To find combinations that exhibit an interaction effect, one filters for promising compound combinations by comparing to a response without interaction. A common principle for no interaction is Loewe Additivity which is based on the assumptio...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00031
更新日期:2018-02-06 00:00:00
abstract::Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a frequently occurring type of nontraumatic osteonecrosis. A failure of the timely treatment can eventually result in the collapse of the subchondral bone structure. Luteolin (Lut), a compound extracted from Rhizoma Drynariae, is reported to possess ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01195
更新日期:2020-08-12 00:00:00
abstract::Pickering emulsion, a kind of emulsion stabilized only by solid particles locating at oil-water interface, has been discovered a century ago, while being extensively studied in recent decades. Substituting solid particles for traditional surfactants, Pickering emulsions are more stable against coalescence and can obta...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00287
更新日期:2017-05-23 00:00:00
abstract::Alzheimer disease (AD) is a progressive and deleterious neurodegenerative disorder that affects mostly the elderly population. At the moment, no effective treatments are available in the market, making the whole situation a compelling challenge for societies worldwide. Recently, novel mechanisms have been proposed to ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00902
更新日期:2019-08-23 00:00:00
abstract::Salvia miltiorrhiza Bunge, a member of the Lamiaceae family, is valued in traditional Chinese Medicine. Its dried root (named Danshen) has been used for hundreds of years, primarily for the treatment of cardiovascular and cerebrovascular diseases. Tanshinones are the main active ingredients in S. miltiorrhiza and exhi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00202
更新日期:2019-03-14 00:00:00
abstract::Neutrophil killing of bacteria is mediated by oxidative and non-oxidative mechanisms. Oxidants are generated through the NADPH oxidase complex, whereas antimicrobial proteins and peptides rank amongst non-oxidative host defenses. Mucus hypersecretion, deficient hydration and poor clearance from the airways are promine...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.554353
更新日期:2020-09-30 00:00:00
abstract::The inhibitors for EGF receptor tyrosine kinase (EGFR-TKIs) such as gefitinib have been used as a standard treatment for non-small cell lung cancer (NSCLC), but the increasingly occurrence of drug resistance, the associated adverse effects and the enrichment of cancer stem cells significantly impedes its clinical appl...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01413
更新日期:2018-11-30 00:00:00
abstract::Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA's anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-defi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00850
更新日期:2019-07-26 00:00:00
abstract::Many ion channels are involved in tumor development, promoting cancer cell proliferation, migration, invasion, and survival. Accordingly, some of them have been suggested as tumor markers and novel targets for cancer therapy. Some sex steroid hormones (SSH), including estrogens and androgens, favor cancer progression....
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.00152
更新日期:2020-02-28 00:00:00
abstract::Random-pattern skin flap replantation is commonly used to repair skin defects during plastic and reconstructive surgery. However, flap necrosis due to ischemia and ischemia-reperfusion injury limits clinical applications. Betulinic acid, a plant-derived pentacyclic triterpene, may facilitate flap survival. In the pres...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01017
更新日期:2019-09-13 00:00:00
abstract::Local people in the Sudhnoti district of Pakistan share a rich practice of traditional medicine for the treatment of a variety of ailments. We selected nine plants from the Sudhnoti ethnopharmacological tradition used for the treatment of infectious and inflammatory disease. Our aim was to evaluate the in vitro anti-i...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00815
更新日期:2018-08-02 00:00:00
abstract::The clinical benefit of therapies using Mesenchymal Stem Cells (MSCs) is attributable to their pleiotropic effect over cells and tissues, mainly through their secretome. This paracrine effect is mediated by secreted growth factors and extracellular vesicles (EV) including small EV (sEV). sEV are extra-cellular, membra...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00679
更新日期:2020-05-21 00:00:00
abstract::Ethanol-induced gastric mucosal injury is a common gastrointestinal disorder. Polysaccharides separated from herbs have been shown to be effective for ethanol-induced gastric mucosal injury, but whether the polysaccharides from Dendrobium officinale Kimura & Migo leaves (LDOP-1) protected mucosa from ethanol-induced i...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.526349
更新日期:2020-11-11 00:00:00
abstract::Patient-derived cell lines and animal models have proven invaluable for the understanding of human intestinal diseases and for drug development although both inherently comprise disadvantages and caveats. Many genetically determined intestinal diseases occur in specific tissue microenvironments that are not adequately...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2016.00334
更新日期:2016-09-22 00:00:00
abstract::The genus Ononis has important value as traditional drugs and foods. In the present work, we aimed to assess the chemical profiles and biological effects of Ononis natrix subsp. hispanica extracts (ethyl acetate, methanol, and water). For chemical profile, total and individual phenolic components were detected. For bi...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00600
更新日期:2017-09-01 00:00:00