Abstract:
:Activating mutations within the tyrosine kinase (TK) domain of epidermal growth factor receptor (EGFR) gene are observed in 10 ~ 30% of the patients diagnosed with non-small cell lung cancer (NSCLC), and are causally related to NSCLC initiation and progression. Treatments with tyrosine kinase inhibitors (TKIs) targeting EGFR significantly improve the outcome of NSCLC patients with EGFR mutation, but are often associated with drug resistance, which is the main cause of treatment failure and cancer relapse. In the present study, by screening the transcriptome of NSCLC patients, we found that EGFR activation is highly correlated with the up-regulation of mitotic regulator, never in mitosis gene A-related kinase 2 (NEK2). NEK2 overexpression is associated with the poor survival of EGFR-mutant patients but not the wild-type patients. Further functional validation revealed that EGFR mutation induces NEK2 expression by activating ERK signaling pathway. Elevated NEK2 level promotes the rapid cell cycle progression and favors the rapid proliferation of EGFR-mutant NSCLC cells. Of note, NEK2 overexpression also impairs the efficacy of TKI treatment via inhibiting apoptosis, while depleting NEK2 suppresses cell growth and restored the sensitivity of TKI in NSCLC cells. Taken together, our study revealed that NEK2 is an oncogene regulated by EGFR mutation and is involved in disease progression and treatment response in NSCLC with EGFR mutation. These findings will pave the road for optimizing personalized treatment strategies to overcome drug resistance and improve the prognosis of lung cancer patients with EGFR mutation.
journal_name
Mol Cell Biochemjournal_title
Molecular and cellular biochemistryauthors
Chen C,Peng S,Li P,Ma L,Gan Xdoi
10.1007/s11010-020-03854-zsubject
Has Abstractpub_date
2020-12-01 00:00:00pages
15-25issue
1-2eissn
0300-8177issn
1573-4919pii
10.1007/s11010-020-03854-zjournal_volume
475pub_type
杂志文章abstract::Three antisera were prepared against non-histone protein classes named NHCP1, NHCP2 and dehistonized chromatin (with different affinity to DNA) from hamster liver. Two main antigenic bands of MW 17,000 and 36,000 were specific in the NHCP1 fraction and one antigen of MW 56,000 was specific for the NHCP2 fraction from ...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF00220720
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abstract::Cardiovascular diseases involve critical mechanisms including impaired nitric oxide (NO) levels and abnormal matrix metalloproteinase (MMP) activity. While NO downregulates MMP expression in some cell types, no previous study has examined whether NO downregulates MMP levels in endothelial cells. We hypothesized that N...
journal_title:Molecular and cellular biochemistry
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journal_title:Molecular and cellular biochemistry
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更新日期:2019-03-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-020-03967-5
更新日期:2020-11-03 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:
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abstract::A sialic acid binding lectin, AchatininH, was purified in single step from the hemolymph of the land snail, Achatina fulica, by the affinity chromatography on sheep submaxillary mucin coupled to Sepharose 4B. The yield of the lectin was found to be 3 mg from 100 ml of hemolymph. The homogeneity of the lectin was estab...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF00214774
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-012-1324-9
更新日期:2012-08-01 00:00:00
abstract::Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an importa...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-017-3115-9
更新日期:2018-01-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-020-04023-y
更新日期:2021-01-15 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-005-3077-1
更新日期:2005-06-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1023/a:1007040705928
更新日期:2000-03-01 00:00:00
abstract::The deiodinases regulate the activation and inactivation of Thyroid hormones (TH), in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2 and DIO3, have different catalytic role and cellular and tissue distribution. Aim of this study is to evaluate a rat model of regional ischemia/reperfu...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-020-03873-w
更新日期:2020-12-01 00:00:00
abstract::When cells of the thymus or mouse leukemias P288 and L1210 are exposed in vitro to the potent synthetic glucocorticoid, 3H-Triamcinolone acetonide, the steroid enters the cells passively and binds to macromolecules in the cytoplasm. At 37 degrees C this hormone-receptor complex enters the nucleus and associates with t...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF01751312
更新日期:1975-12-31 00:00:00
abstract::Nitric oxide (NO) is a messenger molecule which regulates many physiological functions like immunity, vascular tone and serves as a neurotransmitter. Although it is known to participate in healing process, its role in collagen synthesis is not clear. Therefore, the present investigation was done to study the role of N...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1023/a:1006977513146
更新日期:1999-10-01 00:00:00
abstract::The present review is focused on the main achievements realized in the lysozyme research field since the meeting held in 1972 to commemorate the fiftieth anniversary of the discovery of this enzyme. Despite of extensive structural, physico-chemical, crystallographic, genetic, immunological and evolutionary studies dev...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章,评审
doi:10.1007/BF00285225
更新日期:1984-09-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-010-0705-1
更新日期:2011-05-01 00:00:00
abstract::Cytosolic purine nucleoside phosphorylase (PNPase) is a well known, and described enzyme which exists in a variety of organisms, both procaryotic and eucaryotic. More recently this enzyme was found in bovine liver mitochondria. The mitochondrial purine nucleoside phosphorylase was purified 63 fold and has a molecular ...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF00926515
更新日期:1994-06-29 00:00:00
abstract::Telocytes (TCs) are a novel cell type identified among interstitial cells in various organs. TCs are characterized by very long cell processes (tens to hundreds micrometres) named telopodes (Tps) with uneven calibre: dilations (podoms) and very thin segments (podomers). However, little is known about the factors which...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-015-2548-2
更新日期:2015-12-01 00:00:00
abstract::Transport characteristics of essential trace elements as zinc, copper, selenium and iron have been studied in maternal-fetal direction in normal pregnancies, using in vitro perfusion of human placental lobules. Solutions of trace elements corresponding to twice the physiological concentrations were injected (100 micro...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1023/a:1025565720489
更新日期:2003-10-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) have the potential for self-renewal and multipotential differentiation to regenerate damaged tissues or recover functional absence in diseases. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as contrast agents in magnetic resonance imaging (MRI) for labeling cells in vitro a...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-011-0904-4
更新日期:2011-11-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-020-03923-3
更新日期:2020-09-29 00:00:00
abstract::Several peptides derived from microtubule-associated tau protein, have been tested as substrates for glycogen synthase kinase 3 (GSK 3). In the absence of cofactors, GSK 3 can modify serines or threonines followed by prolines. In other cases, a phosphorylation in position +4 is required for the phosphorylation of thre...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF00229744
更新日期:1996-12-06 00:00:00
abstract::Amida was first isolated from a rat hippocampal cDNA library as an Arc-associated protein. Although previous studies have shown that Amida mRNA is predominantly expressed and developmentally regulated in rat testis and overexpression induces apoptosis, the function of Amida remains unclear. In this study, we found tha...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract::The roles of TGF-beta and the interaction between TGF-beta and EGFR signaling are critical in Sertoli cell, though the knowledge about them is limited. RT-PCR was used to characterize the status of TGF-beta signaling in clinical testicular specimens with complete Sertoli cell-only syndrome (SCOS). The mouse Sertoli ce...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-008-9869-3
更新日期:2008-12-01 00:00:00
abstract::Cultured cardiac myocytes were depleted of ATP by incubation with oligomycin (1 mg/ml). Then the ability of the cells to oxidize various substrates and to restore ATP levels was studied. Following ATP depletion, the cells were found to be able to oxidize glucose given alone, but not palmitate. However, with both subst...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF00227544
更新日期:1996-09-20 00:00:00
abstract::Flavonoids are naturally occurring plant compounds with antioxidant properties. Their consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis. Low-density lipoprotein (LDL) oxidative modification is currently thought to be a significant event in...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1023/a:1010944919952
更新日期:2001-05-01 00:00:00
abstract::In this study, we examined changes in the biochemical and inotropic events of the alpha(1)-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism was induced by treating experimental animals with 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 7 weeks. A significant decrease of beta- and an...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-006-2348-9
更新日期:2006-02-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/s11010-007-9496-4
更新日期:2007-10-01 00:00:00
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journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1023/a:1006982028460
更新日期:1999-04-01 00:00:00
abstract::We have investigated the links between electrical excitation and contraction in mammalian heart muscle. Using isolated single cells from adult rat ventricle, a whole-cell voltage-clamp technique and quantitative fluorescence microscopy, we have measured simultaneously calcium current (ICa) and [Ca2+]i (with fura-2). W...
journal_title:Molecular and cellular biochemistry
pub_type: 杂志文章
doi:10.1007/BF00220762
更新日期:1989-09-07 00:00:00