Abstract:
:Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated. Following siRNA screening of 47 upregulated proteins indicated that the knockdown of BMK1 showed the most significant ability to inhibit the proliferation of CIBM resistant cells. It was found that phosphorylation of BMK1 was enhanced in resistant cells, which suggested an association of BMK1 with drug resistance. Further study indicated that phospho-activation of BMK1 by MEK5D enhanced the resistance to CIBM. Conversely, inhibition of BMK1 by shRNAi or BMK1 inhibitor (XMD8-92) impaired not only the acquirement of resistance to CIBM, but also the proliferation of CIBM resistant cells. Further kinome-scale siRNA screening demonstrated that SRC\MEK5 cascade promotes the phospho-activation of BMK1 in response to CIBM. Our study not only provides a global phosphoproteomic view of CIBM in melanoma, but also demonstrates that inhibition of BMK1 has therapeutic potential for the treatment of melanoma.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Song C,Wang L,Xu Q,Wang K,Xie D,Yu Z,Jiang K,Liao L,Yates JR,Lee JD,Yang Qdoi
10.1038/srep46244subject
Has Abstractpub_date
2017-04-07 00:00:00pages
46244issn
2045-2322pii
srep46244journal_volume
7pub_type
杂志文章abstract::Congenital reproductive tract anomalies could impair fertility. Female and male reproductive tracts are developed from Müllerian ducts and Wolffian ducts, respectively, involving initiation, elongation and differentiation. Genetic basis solely for distal reproductive tract development is largely unknown. Lhfpl2 (lipom...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep23037
更新日期:2016-03-11 00:00:00
abstract::Afforestation is an important approach to mitigate global warming. Its complex interactions with the climate system, however, makes it controversial. Afforestation is expected to be effective in the tropics where biogeochemical and biogeophysical effects act in concert; however, its potential in the large semi-arid re...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-19265-6
更新日期:2018-01-17 00:00:00
abstract::Nutrient resorption processes in the plants infected by pathogen remain poorly understood. Huanglongbing (HLB) is a destructive disease of citrus. HLB-pathogen 'Candidatus Liberibacter asiaticus' grows specifically in the phloem of hosts and may cause problems in the plant vascular system after infection. Therefore, i...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep14675
更新日期:2015-09-30 00:00:00
abstract::The expression of aminoglycoside-modifying enzymes represents a survival strategy of antibiotic-resistant bacteria. Aminoglycoside 2'-N-acetyltransferase [AAC(2')] neutralizes aminoglycoside drugs by acetylation of their 2' amino groups in an acetyl coenzyme A (CoA)-dependent manner. To understand the structural featu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-78699-z
更新日期:2020-12-09 00:00:00
abstract::Affinity maturation is one of the cardinal strategies for improving antibody function using in vitro evolutionary methods; one such well-established method is phage display. To minimise gene deletion, we previously developed an open sandwich (OS) method wherein selection was performed using only phage-displaying VH fr...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-23796-3
更新日期:2018-04-03 00:00:00
abstract::Low back pain (LBP) is a widespread debilitating disorder of significant socio-economic importance and intervertebral disc (IVD) degeneration has been implicated in its pathogenesis. Despite its high prevalence the underlying causes of LBP and IVD degeneration are not well understood. Recent work in musculoskeletal de...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-12666-z
更新日期:2017-10-02 00:00:00
abstract::The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported in DED patients. We hypothesized that physical and psychological stressors impair tear secretion. To examine the relationship between stress loading a...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-39467-w
更新日期:2019-03-04 00:00:00
abstract::Breast cancer in young women is typically with higher proportion of adverse pathological features. Breast cancer with BRCA1 mutation is often early-onset, and is usually associated with triple negative phenotpe. In this study, we aim to analyze the clinicopathological characteristics and prognosis in young breast canc...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep05360
更新日期:2014-06-19 00:00:00
abstract::This study investigates the effect of Repetitive Transcranial Magnetic Stimulation (rTMS) on persistent post-concussion syndrome (PCS). The study design was a randomized (coin toss), placebo controlled, and double-blind study. Thirty-seven participants with PCS were assessed for eligibility; 22 were randomised and 18 ...
journal_title:Scientific reports
pub_type: 杂志文章,随机对照试验
doi:10.1038/s41598-019-41923-6
更新日期:2019-04-02 00:00:00
abstract::In the Brown et al. study 'Increased food supply mitigates ocean acidification effects on calcification but exacerbates effects on growth' they show disagreement with the tested hypothesis and data analysis methodology used in our 2016 study. We acknowledge careful criticism and a constructive dialogue are necessary t...
journal_title:Scientific reports
pub_type: 评论,杂志文章
doi:10.1038/s41598-018-27670-0
更新日期:2018-06-28 00:00:00
abstract::Protein kinases are enzymes whose abundance, protein-protein interactions, and posttranslational modifications together determine net signaling activity in cells. Large-scale data on cellular kinase activity are limited, because existing assays are cumbersome, poorly sensitive, low throughput, and restricted to measur...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-55998-8
更新日期:2019-12-19 00:00:00
abstract::Although graphene is a typical two dimensional materials, it has converted to multi-dimensional materials with many unique properties. As an example, the one dimensional graphene fiber is fabricated by utilizing ionic liquid as coagulation and functional diamines as cross-linkers to connect graphene oxide layers. The ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep29534
更新日期:2016-07-08 00:00:00
abstract::Contrast-induced nephropathy (CIN) has become the third-leading cause of hospital-acquired acute renal injury. Although alprostadil has been proposed as an effective preventative measure, this conclusion remains inconsistent. Thus, we performed a meta-analysis of the published studies on this topic to evaluate the pre...
journal_title:Scientific reports
pub_type: 杂志文章,meta分析
doi:10.1038/s41598-017-01160-1
更新日期:2017-04-21 00:00:00
abstract::The availability and spatial distribution of food resources affect animal behavior and survival. Black howler monkeys (Alouatta pigra) have a foraging strategy to balance their nutrient intake that involves mixing their consumption of leaves and fruits. The spatial aggregation of food items should impact this strategy...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-55932-y
更新日期:2019-12-19 00:00:00
abstract::Virtual planning of open cranial vault reconstruction is used to simulate and define an pre-operative plan for craniosynostosis surgery. However, virtual planning techniques are subjective and dependent on the experience and preferences of the surgical team. To develop an objective automated 3D pre-operative planning ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-21662-w
更新日期:2018-02-20 00:00:00
abstract::Channelrhodopsins are light-gated ion channels of green algae used for the precise temporal and spatial control of transmembrane ion fluxes. The channelrhodopsin Chrimson from Chlamydomonas noctigama allows unprecedented deep tissue penetration due to peak absorption at 590 nm. We demonstrate by electrophysiological r...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-09600-8
更新日期:2017-08-30 00:00:00
abstract::Small heat shock proteins are ubiquitous molecular chaperones that form the first line of defence against the detrimental effects of cellular stress. Under conditions of stress they undergo drastic conformational rearrangements in order to bind to misfolded substrate proteins and prevent cellular protein aggregation. ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep24019
更新日期:2016-04-07 00:00:00
abstract::The metabolic health effects of vitamin A and E nutritional status in early life are largely unknown. We assessed whether vitamin A and vitamin E nutritional status may affect circulating leptin, adiponectin, insulin-like growth factor (IGF)-I and IGF-II levels in early life in humans. In a singleton birth cohort (n =...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-18531-3
更新日期:2018-01-08 00:00:00
abstract::The quantum mechanical motion of electrons and nuclei in systems spatially confined to the molecular dimensions occurs on the sub-femtosecond to the femtosecond timescales respectively. Consequently, the study of ultrafast electronic and, in specific cases, nuclear dynamics requires the availability of light pulses wi...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-60331-9
更新日期:2020-02-28 00:00:00
abstract::Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of react...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/srep43441
更新日期:2017-02-27 00:00:00
abstract::Previous studies reported that boreal winter precipitation in southeastern China (SEC) tends to increase during El Niño. In this study, however, we find that most weak El Niño events are accompanied by below-normal precipitation in SEC, although strong El Niño events are accompanied by above-normal precipitation in SE...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-53496-5
更新日期:2019-11-22 00:00:00
abstract::Enterovirus A71 (EV-A71), which belongs to the family Picornaviridae, can invade the central nervous system (CNS) and cause severe CNS complications or death. The EV-A71 antigen has been detected in the neurons in the brains of humans who died from EV-A71 infection. However, the effect of EV-A71 infection on human neu...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-71970-3
更新日期:2020-09-17 00:00:00
abstract::Ultra-high resolution optical coherence tomography (UHR-OCT) can image the corneal epithelium and Bowman's layer and measurement the thicknesses. The purpose of this study was to validate the diagnostic power of vertical thickness profiles of the corneal epithelium and Bowman's layer imaged by UHR-OCT in the diagnosis...
journal_title:Scientific reports
pub_type: 临床试验,杂志文章
doi:10.1038/srep31550
更新日期:2016-08-11 00:00:00
abstract::Soil heavy metals exhibit significant spatiotemporal variability and are strongly correlated with other soil heavy metals. Thus, other heavy metals can be used to improve the accuracy of predictions when performing spatiotemporal predictions of soil heavy metals within a given area. In this study, we propose the spati...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-17018-5
更新日期:2017-12-01 00:00:00
abstract::Awe, a complex emotion composed by the appraisal components of vastness and need for accommodation, is a profound and often meaningful experience. Despite its importance, psychologists have only recently begun empirical study of awe. At the experimental level, a main issue concerns how to elicit high intensity awe exp...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-017-01242-0
更新日期:2017-04-27 00:00:00
abstract::Cosolvent Molecular Dynamics (MD) simulations are increasingly popular techniques developed for prediction and characterization of allosteric and cryptic binding sites, which can be rendered "druggable" by small molecule ligands. Despite their conceptual simplicity and effectiveness, the analysis of cosolvent MD traje...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-55394-2
更新日期:2019-12-13 00:00:00
abstract::Organic-inorganic halide perovskite nanocrystals or quantum dots (PQDs) are excellent candidates for optoelectronic applications, such as lasers, solar cells, light emitting diodes, and single photon sources. However, the potential applications of PQDs can expand once the photoluminescence, and in particular, the blin...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-020-58926-3
更新日期:2020-02-07 00:00:00
abstract::Bacteremia caused by MRSA with reduced vancomycin susceptibility (MRSA-RVS) frequently resulted in treatment failure and mortality. The relation of bacterial factors and unfavorable outcomes remains controversial. We retrospectively reviewed clinical data of patients with bacteremia caused by MRSA with vancomycin MIC ...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-018-26277-9
更新日期:2018-05-18 00:00:00
abstract::Knowing when, where, and how seizures are initiated in large-scale epileptic brain networks remains a widely unsolved problem. Seizure precursors - changes in brain dynamics predictive of an impending seizure - can now be identified well ahead of clinical manifestations, but either the seizure onset zone or remote bra...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-47092-w
更新日期:2019-07-23 00:00:00
abstract::The endo-levanase BT1760 of a human gut commensal Bacteroides thetaiotaomicron randomly cuts a β-2,6-linked fructan, levan, into fructo-oligosaccharides providing a prebiotic substrate for gut microbiota. Here we introduce the crystal structure of BT1760 at resolution of 1.65 Å. The fold of the enzyme is typical for G...
journal_title:Scientific reports
pub_type: 杂志文章
doi:10.1038/s41598-019-44785-0
更新日期:2019-06-11 00:00:00