Cell Host & Microbe
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2024
·
IF 20.6
Pingmei Huang,Fenfen Ji,Alvin Ho-Kwan Cheung,Kaili Fu,Qiming Zhou,Xiao Ding,Danyu Chen,Yufeng Lin,Luyao Wang,Ying Jiao,Eagle S.H. Chu,Wei Kang,Ka Fai To,Jun Yu,Chi Chun Wong
Peptostreptococcus stomatis ( P. stomatis ) is enriched in colorectal cancer (CRC), but its causality and translational implications in CRC are unknown. Here, we show that P. stomatis accelerates colonic tumorigenesis in Apc Min/+ and azoxymethane/dextran sodium sulfate (AOM-DSS) models by inducing cell proliferation, suppressing apoptosis, and impairing gut barrier function. P. stomatis adheres to CRC cells through its surface protein fructose-1,6-bisphosphate aldolase (FBA) that binds to the integrin α6/β4 receptor on CRC cells, leading to the activation of ERBB2 and the downstream MEK-ERK-p90 cascade. Blockade of the FBA-integrin α6/β4 abolishes ERBB2-mitogen-activated protein kinase (MAPK) activation and the protumorigenic effect of P. stomatis . P. stomatis -driven ERBB2 activation bypasses receptor tyrosine kinase (RTK) blockade by EGFR inhibitors (cetuximab, erlotinib), leading to drug resistance in xenograft and spontaneous CRC models of KRAS-wild-type CRC. P. stomatis also abrogates BRAF inhibitor (vemurafenib) efficacy in BRAF V600E -mutant CRC xenografts. Thus, we identify P. stomatis as an oncogenic bacterium and a contributory factor for non-responsiveness to RTK inhibitors in CRC.
研究领域:
肿瘤学
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微生物学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2017
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IF 7.78
Xingxin Wang,Dongshu Du,Haibin Dong,Sunfengda Song,Kwangnak Koh,Hongxia Chen
Nanoparticle (NP) structure, compositing and the nature of the NP-functionalized electrode interface have a strong influence upon electrochemical properties that are critical in applications such as sensing, photocatalysis and electrocatalysis . Existing methods to fabricate NP-functionalized electrodes do not allow or precise control over all these variables, especially the NP-electrode interface, making it difficult to understand and predict how structural changes influence electrode activity and consequently limit the application. To conquer this problem, in this study, we fabricated a stepwise construction of a novel supramolecular stabilized gold nanoparticles (AuNPs) multilayer mediated by guest molecules, yielding 3D AuNPs assembly at the electrode interface. para -Sulfonatocalix[4]arene (pSC 4 ), a water soluble macrocyclic synthetic receptor, has been served as a stabilizing ligand for preparation and gaining new insights into pSC 4 stabilized gold nanoparticles (pSC 4 -AuNPs) tethered on the electrode interface through host-guest interaction. We investigated the electrochemical properties of multilayer pSC 4 -AuNPs modified gold electrode using different core size of AuNPs with varying layer number. The electron transfer ability was characterized by electrochemical impedance spectroscopy (EIS). Electrochemical signals are significantly enhanced through the layer-by-layer assembly of pSC 4 -AuNPs due to its high conductivity and high effective area. With this innovative method, by taking the assay of a tumor marker as an example, human epidermal growth factor receptor 2 (ErbB2) was successfully measured with a detection limit of 0.5 ng/mL. Taking the advantage of the pSC 4 -AuNPs multilayer's good biocompatibility , high effective area and high electronic transmission, 3D AuNPs multilayer produced on the electrode interface suggests a portable synthetic pathway for the application into sensitive electrochemical biosensor .
研究领域:
纳米技术
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电化学
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生物传感器
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材料科学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
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IF 5.7
Yuehua Yu,Zixuan Li,Yuan He,Ji Huang,Zhenxiao Sun
Lung adenocarcinoma is a highly fatal carcinoma worldwide with limited therapeutic options. We identified EGFR/ERBB2 as promising dual targets through integrative analysis of clinical data and TCGA database. Molecular docking and cytotoxicity screening of FDA-approved drugs identified Ebastine as a potent dual-targeting agent. Ebastine significantly inhibited NCI-H1975 cell viability (EGFR-mutant with high EGFR/ERBB2 expression), induced ROS elevation, decreased mitochondrial membrane integrity, and triggered apoptosis. Western blot revealed that Ebastine suppressed phosphorylation of EGFR, ERBB2, ERK1/2 and AKT. In xenograft models, Ebastine significantly inhibited NCI-H1975 tumor growth with no significant impact on body weight. Histopathological and immunohistochemical analyses showed reduced Ki67 expression and increased tumor cell apoptosis in Ebastine-treated tumors. Notably, Ebastine promoted macrophage infiltration and M1 polarization both in vivo and in vitro . Our findings establish Ebastine as a promising therapeutic candidate for EGFR/ERBB2-mutant lung adenocarcinoma through a unique dual-targeting approach that combines direct tumor cell inhibition with enhancement of anti-tumor immunity.
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Integrative Medicine
·
2022
·Vol. 29
·期 3
·244-252
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IF 2.626
Wang Yuan-chun,Hui Jian-rong,Xiao Gang,Ma Qiao-lin
Objective To investigate the mechanism of the effect of Astragalus membranaceus ( A. membranaceus ) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach. Methods The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of “ingredient-target” and “ingredient-target-pathway-disease” were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus . Results A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus , kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot. Conclusion Our finding unraveled that an active ingredient of A. membranaceus , quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.
研究领域:
药理学
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肿瘤学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
CANCER LETTERS
·
2023
·
IF 9.7
Xiaosong Wei,Beibei Wang,Zixin Wu,Xiaoming Yang,Yufeng Guo,Yang Yang,Zhiwei Fang,Chengzhi Yi,Liuhui Zhang,Xin Fan,Lirong Zhang,Dongkui Song
One of the most abundant protein-protein interaction domains in the human proteome is the WD40 repeat (WDR) domain. A Gene Expression Omnibus dataset revealed 37 differentially expressed WDR domain genes in bladder cancer (BC). WD repeat domain 54 ( WDR54 ), an upregulated WDR domain gene, was selected for further investigation. Sixty pairs of frozen BC tumor and non-malignant bladder tissues and 83 paraffin-embedded BC tissue specimens were obtained. Loss-/gain-of-function experiments were carried out using BC and xenograft tumor models. WDR54 was overexpressed in BC cells, and its high expression was linked to tumor stage and lymph node metastases in patients. WDR54 contributed to the tumorigenesis and metastasis of BC and impaired its chemosensitivity. WDR54 prevented the degradation and ubiquitination of the mediator of ErbB2-driven cell motility 1 (MEMO1). WDR54 also promoted the interaction between MEMO1 and insulin receptor substrate 1 (IRS1) and activated the IRS1/AKT/β-catenin pathway in BC cells. Particularly, WDR54 depended on MEMO1 to exert its biological functions. Our study demonstrated the relevance of WDR54 in BC and provides insight into the molecular mechanism underlying BC.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-12
·
IF 16.6
Chen Zhigang,Zhang Yi,Li Wenlu,Gao Chenyi,Huang Fengbo,Cheng Lu,Jin Menglei,Xu Xiaoming,Huang Jian
Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms ( ERBB2 , BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 3
·1473-1483
·
IF 2.784
Jun Fu,Luhua Yu,Jie Luo,Rui Huo,Bing Zhu
The purpose of the present study was to analyze the association between paeonol and the known genes related to gastric cancer (GC) using bioinformatics methods, and to investigate the role of paeonol in the potential impact on the nuclear factor‑κB (NF‑κB) signaling pathway, in order to provide a theoretical basis for further elucidating the effect of paeonol on cancer cells. Cell viability, morphology and apoptosis were detected using an MTT assay, an inverted microscope, and flow cytometry, respectively. The correlation between drugs and genes was analyzed using the Search Tool for Interactions of Chemicals (STITCH) gene‑drug interaction network. The expression levels of related mRNA and proteins were determined using reverse transcription‑quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assay. The changes in protein expression were examined using western blot analysis. The correlation network between target genes directly affected by paeonol and known GC genes was determined by analyzing the association between the compounds and genes recorded in the STITCH database. The GC‑related epidermal growth factor receptor 2 (ERBB2) gene was at the core position of the paeonol interaction network and may be an important potential target gene for the effect of paeonol on cancer cells. The effect of paeonol on the viability of the SGC‑7901 GC cell line was detected using an MTT assay, which showed that the inhibitory effect occurred in a time‑ and dose‑dependent manner. The observations of cell morphology demonstrated that the cells were floating, abnormal in shape, had unclear boundaries and were sparse in arrangement following paeonol treatment. Flow cytometry indicated that paeonol significantly accelerated the apoptotic rate of the SGC‑7901 GC cells. The examination of clinical samples suggested that ERBB2 was expressed at a high level in GC samples, and was significantly downregulated following the addition of paeonol. The western blot analysis revealed that downregulating ERBB2 affected the activation of the NF‑κB signaling pathway, thereby upregulating the pro‑apoptotic factor B‑cell lymphoma‑associated X protein. Taken together, paeonol significantly downregulated ERBB2 and inhibited the activation of the NF‑κB signaling pathway, thereby inhibiting the proliferation of SGC‑7901 cells and inducing apoptosis.
研究领域:
肿瘤学
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药理学
·
分子生物学
·
生物信息学
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DOI
PubMed
高影响因子
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