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1.
Cell Death Dis ; 11(4): 230, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286266

RESUMO

Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma (GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMP-dependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.

2.
J Exp Clin Cancer Res ; 39(1): 44, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111229

RESUMO

BACKGROUND: FK506-binding protein 9 (FKBP9) is amplified in high-grade gliomas (HGGs). However, the roles and mechanism(s) of FKBP9 in glioma are unknown. METHODS: The expression of FKBP9 in clinical glioma tissues was detected by immunohistochemistry (IHC). The correlation between FKBP9 expression levels and the clinical prognosis of glioma patients was examined by bioinformatic analysis. Glioblastoma (GBM) cell lines stably depleted of FKBP9 were established using lentiviruses expressing shRNAs against FKBP9. The effects of FKBP9 on GBM cells were determined by cell-based analyses, including anchorage-independent growth, spheroid formation, transwell invasion assay, confocal microscopy, immunoblot (IB) and coimmunoprecipitation assays. In vivo tumor growth was determined in both chick chorioallantoic membrane (CAM) and mouse xenograft models. RESULTS: High FKBP9 expression correlated with poor prognosis in glioma patients. Knockdown of FKBP9 markedly suppressed the malignant phenotype of GBM cells in vitro and inhibited tumor growth in vivo. Mechanistically, FKBP9 expression induced the activation of p38MAPK signaling via ASK1. Furthermore, ASK1-p38 signaling contributed to the FKBP9-mediated effects on GBM cell clonogenic growth. In addition, depletion of FKBP9 activated the IRE1α-XBP1 pathway, which played a role in the FKBP9-mediated oncogenic effects. Importantly, FKBP9 expression conferred GBM cell resistance to endoplasmic reticulum (ER) stress inducers that caused FKBP9 ubiquitination and degradation. CONCLUSIONS: Our findings suggest an oncogenic role for FKBP9 in GBM and reveal FKBP9 as a novel mediator in the IRE1α-XBP1 pathway.

3.
J Org Chem ; 85(6): 4047-4057, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32130006

RESUMO

A series of bifunctional asymmetric phase-transfer catalysts containing novel fluorine-containing urea groups derived from cinchona alkaloids have been synthesized and successfully applied in the asymmetric intramolecular Mannich reaction. The 4-azaindoline products bearing multiple substrates were obtained in excellent yield (90-99%), with high enantioselectivity (up to 95%) and diastereoselectivity (up to >99:1).

4.
Talanta ; 209: 120357, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892081

RESUMO

Mass spectrometry imaging can effectively detect and reflect the information of molecular spatial distribution, and has been widely used for in situ analysis of endogenous or exogenous molecules in organisms. The present work applied the atmospheric pressure matrix-assisted laser desorption ionization mass spectrometry (AP-MALDI-MS) in the imaging of whole zebrafish slices exposed to fipronil. The chemical fingerprints in the range of m/z 600-950 showed significant differences in phospholipids between the fipronil exposed and untreated zebrafish groups. The major perturbed phospholipids were identified as PC(34:2), PC(34:1), PC(34:2)+Na, PC(36:4), PC(38:6), and PS(18:0/22:6), PI(18:0/20:4), PI(18:1/20:4) etc. Our results indicated that the exposure of fipronil obviously affected the phospholipid metabolism of zebrafish, especially of the fish eye region. Our work provides a new method or possibility for toxicological study and related metabolic analysis of pesticides in animals.

5.
Org Lett ; 21(14): 5719-5724, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31265315

RESUMO

N,N'-Acetals are sensitive compounds, and the challenging asymmetric synthesis of acyclic N,N'-acetals by the general addition of amines to ketimines has never been reported so far. In this study, highly enantioselective addition of aryl amines to isatin-derived ketimines catalyzed by chiral urea derived from quinine was developed. A series of new acyclic N,N'-acetals were constructed by this protocol in high to excellent yields (78-99%) and high to excellent enantioselectivities (76-96% ee).

6.
Nucleic Acids Res ; 47(15): 8239-8254, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31216022

RESUMO

XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here, we report POLR2A, the largest catalytic subunit of RNA polymerase II, as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT-based quantitative proteomics identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11 of XAB2 were critical for POLR2A expression by interacting with SNW1. Finally, we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.


Assuntos
Senescência Celular/genética , RNA Polimerases Dirigidas por DNA/genética , Íntrons/genética , Fatores de Transcrição/genética , Transcrição Genética , Linhagem Celular , Linhagem Celular Tumoral , RNA Polimerases Dirigidas por DNA/metabolismo , Células HEK293 , Células HeLa , Humanos , Interferência de RNA , Processamento de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
7.
J Environ Manage ; 242: 327-342, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054397

RESUMO

This paper contributes to our understanding of how to improve manufacturing firms' green operations underpinned by the proactive behavior theory. Chinese manufacturing firms are focused on because of their significant impact on global climate change and distinctive governance structure. Specifically, we survey 155 highest-level environmental managers (EMs) in these firms who have an ultimate decision-making power on environmental issues, and investigate the antecedents and consequence of their proactive pollution reduction behavior (PPRB). Through identifying the psychological motivation implied in EMs' environmental management behavior, we find that both EMs' role breadth self-efficacy (including in-role self-efficacy and extra-role self-efficacy) and felt responsibility (including felt responsibility establishment and felt responsibility coordination) can improve their PPRB. Further, available resources in firms only positively moderate the impact of extra-role self-efficacy on PPRB, and incentives from external stakeholders only moderate the impact of felt responsibility establishment on PPRB. Our empirical results also confirm that PPRB can improve corporate operational performance, strategic competitiveness, and environmental performance, but a higher level of PPRB's performance comes more from the driving force of PPRB's antecedents rather than PPRB itself.


Assuntos
Comércio , Poluição Ambiental , Motivação
8.
Sci Total Environ ; 670: 478-485, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30904659

RESUMO

For a better understanding of the migration process of trace metals in aquatic environment with multiple phases, dynamic processes of Cd reaching quasi-equilibrium among different phases, including water, natural biofilms and surficial sediments, were investigated, using microcosmic simulating systems. The processes of the re-equilibrium of Cd after a supplement of Cd and after an adjustment of solution pH were also investigated. The results showed both the migration of Cd from water to the solid materials, and the accumulation of Cd in the solid materials. (Modified) pseudo-second-order kinetic model can be used to simulate such processes. However, Cd content in biofilms and sediments varied in different ways: Cd in biofilms increased rapidly at first, then decreased, and finally approached constancy, while Cd in sediments increased slowly and continuously. The more the Cd was added in the water, the higher the Cd contents in solid phases, and the quicker the Cd accumulation and decrease process would be. The decrease of solution pH promoted the release of adsorbed Cd from the solid phases, especially from biofilms, while the increase of pH stimulated the migration of Cd to the solids. Therefore, as an indicator and temporary reservoir of trace metals in water, which respond rapidly to the variation of trace metal concentration in water, biofilms play a role in indicating and buffering the variation of trace metals in water. Although the response of sediments to the variation of metal concentration in water is very slow, most trace metals migrate to sediments eventually, thus sediments play a role as a more stable and massive reservoir for trace metals in water.


Assuntos
Biofilmes/crescimento & desenvolvimento , Cádmio/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Adsorção , Biodegradação Ambiental
9.
J Clin Invest ; 129(3): 1030-1046, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30688660

RESUMO

Chronic stress triggers activation of the sympathetic nervous system and drives malignancy. Using an immunodeficient murine system, we showed that chronic stress-induced epinephrine promoted breast cancer stem-like properties via lactate dehydrogenase A-dependent (LDHA-dependent) metabolic rewiring. Chronic stress-induced epinephrine activated LDHA to generate lactate, and the adjusted pH directed USP28-mediated deubiquitination and stabilization of MYC. The SLUG promoter was then activated by MYC, which promoted development of breast cancer stem-like traits. Using a drug screen that targeted LDHA, we found that a chronic stress-induced cancer stem-like phenotype could be reversed by vitamin C. These findings demonstrated the critical importance of psychological factors in promoting stem-like properties in breast cancer cells. Thus, the LDHA-lowering agent vitamin C can be a potential approach for combating stress-associated breast cancer.


Assuntos
Neoplasias da Mama/enzimologia , Epinefrina/metabolismo , L-Lactato Desidrogenase/metabolismo , Células-Tronco Neoplásicas/enzimologia , Estresse Psicológico/metabolismo , Animais , Ácido Ascórbico/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/patologia
10.
J Sep Sci ; 42(1): 330-341, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30444314

RESUMO

Pesticides, widely applied in agriculture, can produce a variety of transformation products and their continuous use causes deleterious effects to ecosystem. Efficient and sensitive analytical techniques for enrichment and analysis of pesticides samples are highly required. Compared with other extraction methods, solid-phase micro extraction is a solvent free, cost effective, robust, versatile, and high throughput sample preparation technique, especially for the analysis of pesticides from complicated matrices. Coupling of solid-phase micro extraction with gas chromatography and mass spectrometry and liquid chromatography-mass spectrometry has been extensively applied in pesticide analysis. On the other hand, in recent years, combination of fast separation using solid-phase micro extraction and rapid detection using ambient mass spectrometry is providing highly efficient pesticide screening. This article summarizes the applications of solid-phase micro extraction coupled to mass spectrometry for pesticides analysis.

11.
Org Biomol Chem ; 16(46): 8927-8932, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30431642

RESUMO

A highly diastereo- and enantioselective Mannich reaction of isatin-derived ketimines with oxo-indanecarboxylates catalyzed by chiral thiourea derived from hydroquinidine has been developed. A series of 3-substituted 3-amino-oxindoles containing assembled bicyclic rings linked by a C-C bond were constructed by this protocol in excellent yields (92-99%) with high enantioselectivities (85-99% ee) and diastereoselectivities (up to >99 : 1 dr).

12.
J Exp Clin Cancer Res ; 37(1): 165, 2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30041665

RESUMO

BACKGROUND: Aberrant activation of ß-catenin and Yes-associated protein (YAP) signaling pathways has been associated with hepatocellular carcinoma (HCC) progression. The LIM domain protein Ajuba regulates ß-catenin and YAP signaling and is implicated in tumorigenesis. However, roles and mechanism of Ajuba expression in HCC cells remain unclear. The E3 ligase Hakai has been shown to interact with other Ajuba family members and whether Hakai interacts and regulates Ajuba is unknown. METHODS: HCC cell lines stably depleted of Ajuba or Hakai were established using lentiviruses expressing shRNAs against Ajuba or Hakai. The effects of Ajuba on HCC cells were determined by a number of cell-based analyses including anchorage-independent growth, three dimension cultures and trans-well invasion assay. In vivo tumor growth was determined in a xenograft model and Ajuba expression in tumor sections was examined by immunohistochemistry. Co-immunoprecipitation, confocal microscopy and immunoblot assay were used to examine the expression and interaction between Ajuba and Hakai. RESULTS: Depletion of Ajuba in HCC cells significantly enhanced anchorage-independent growth, invasion, the formation of spheroids and tumor growth in a xenograft model, suggesting a tumor suppressor function for Ajuba in HCC. Mechanistically, Ajuba depletion triggered E-cadherin loss and ß-catenin translocation with increased Cyclin D1 levels. In addition, depletion of Ajuba upregulated the levels of YAP and its target gene CYR61. Furthermore, siRNA-mediated knockdown of either ß-catenin or YAP attenuated the pro-tumor effects by Ajuba depletion on HCC cells. Notably, Ajuba stability in HCC cells was regulated by Hakai, an E3 ligase for E-cadherin. Hakai interacted with Ajuba via its HYB domain and induced Ajuba neddylation, which was antagonized by the neddylation inhibitor, MLN4924, but not MG132. We further show that overexpression of Hakai in HCC cells markedly increased anchorage-independent growth, spheroid-formation ability and tumor growth in xenografts whereas Hakai depletion resulted in these opposite effects, indicating an oncogenic role for Hakai in HCC. Hakai also induced ß-catenin translocation with increased levels of Cyclin D1. CONCLUSIONS: Our data suggest a role for Ajuba and Hakai in HCC, and uncover the mechanism underlying the regulation of Ajuba stability.


Assuntos
Carcinoma Hepatocelular/genética , Proteínas com Domínio LIM/genética , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligases/metabolismo , beta Catenina/metabolismo , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Proteínas com Domínio LIM/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Nus , Transfecção
13.
J Org Chem ; 83(3): 1486-1492, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29271656

RESUMO

An efficient enantioselective aza-Henry reaction of aryl α-ketoester-derived ketimines has been realized by using bifunctional thiourea-ammonium salt phase-transfer catalysts, which were derived from quinine. A variety of aryl α-ketoester-derived N-Ts ketimines were investigated, and the corresponding products were obtained in high to excellent yields (up to 99%) with good to high enantioselectivities (up to >99% ee).


Assuntos
Compostos de Amônio/química , Alcaloides de Cinchona/química , Iminas/química , Nitrilos/química , Tioureia/química , Catálise , Estrutura Molecular , Sais/química , Estereoisomerismo
14.
Org Biomol Chem ; 15(43): 9234-9242, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29085949

RESUMO

New quaternary ammonium types of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors derived from α-amino acids were readily prepared and found to be highly efficient in the asymmetric nitro-Mannich reactions of amidosulfones. Very broad substrate generality was observed, and the products were achieved in high enantio-/diastereoselectivities (90->99.9% ee, 90 : 10 to 92 : 8 dr). Compared with previous reports, the enantioselectivity of aliphatic amidosulfones has been improved to a high level (91-93% ee).


Assuntos
Aminoácidos/química , Nitrocompostos/química , Catálise , Ligação de Hidrogênio , Estereoisomerismo
15.
Mol Med Rep ; 16(5): 5954-5964, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28849102

RESUMO

As the predominant thyroid cancer, papillary thyroid cancer (PTC) accounts for 75­85% of thyroid cancer cases. This research aimed to investigate transcriptomic changes and key genes in PTC. Using RNA­sequencing technology, the transcriptional profiles of 5 thyroid tumor tissues and 5 adjacent normal tissues were obtained. The single nucleotide polymorphisms (SNPs) were identified by SAMtools software and then annotated by ANNOVAR software. After differentially expressed genes (DEGs) were selected by edgR software, they were further investigated by enrichment analysis, protein domain analysis, and protein­protein interaction (PPI) network analysis. Additionally, the potential gene fusion events were predicted using FusionMap software. A total of 70,172 SNPs and 2,686 DEGs in the tumor tissues, as well as 83,869 SNPs in the normal tissues were identified. In the PPI network, fibronectin 1 (FN1; degree=31) and transforming growth factor ß receptor 1 (TGFßR1; degree=22) had higher degrees. A total of 7 PPI pairs containing the non­synonymous risk SNP loci in the interaction domains were identified. Particularly, the interaction domains involved in the interactions of FN1 and 5 other proteins (such as FN1­tenascin C, TNC) had non­synonymous risk SNP loci. Furthermore, 11 and 4 gene fusion events were identified in all of the tumor tissues and normal tissues, respectively. Additionally, the NK2 homeobox 1­surfactant associated 3 (NKX2­1­SFTA3) gene fusion was identified in both tumor and normal tissues. These results indicated that TGFßR1 and the NKX2­1­SFTA3 gene fusion may be involved in PTC. Furthermore, FN1 and TNC containing the non­synonymous risk SNP loci might serve a role in PTC by interacting with each other.


Assuntos
Carcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/genética , Proteínas Associadas a Surfactantes Pulmonares/genética , Neoplasias da Glândula Tireoide/genética , Fator Nuclear 1 de Tireoide/genética , Transcriptoma , Adulto , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Citocinas/genética , Citocinas/metabolismo , Feminino , Fibronectinas , Perfilação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Excisão de Linfonodo , Linfonodos/metabolismo , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Proteínas de Fusão Oncogênica/metabolismo , Polimorfismo de Nucleotídeo Único , Mapeamento de Interação de Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Tenascina/genética , Tenascina/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Fator Nuclear 1 de Tireoide/metabolismo , Tireoidectomia
16.
Water Sci Technol ; 75(11-12): 2538-2545, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28617272

RESUMO

Ammonia nitrogen (NH4-N) contaminated wastewater has posed a great threat to the safety of water resources. In this study, air stripping was employed to remove and recover NH4-N from acetylene purification wastewater (APW) in a polyvinylchloride manufacturing plant. Investigated parameters were initial APW pH, air flow rate, APW temperature and stripping time. The NH4-N removal by air stripping has been modeled and the overall volumetric mass transfer coefficient (KLa) of the stripping process has been calculated from the model equation obtained. In addition, the ability of H2SO4 solution to absorb the NH3 stripped was also investigated. The results indicated that under the experimental conditions, the APW temperature and its initial pH had significant effects on the NH4-N removal efficiency and the KLa, while the effects of other factors were relatively minor. The removal efficiency and residual concentration of NH4-N were about 91% and 12 mg/L, respectively, at the optimal operating conditions of initial APW pH of 12.0, air flow rate of 0.500 m3/(h·L), APW temperature of 60 °C and stripping time of 120 min. One volume of H2SO4 solution (0.2 mol/L) could absorb about 93% of the NH3 stripped from 54 volumes of the APW.


Assuntos
Amônia/análise , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Acetileno/química , Resíduos Industriais , Águas Residuárias/química
18.
J Org Chem ; 82(9): 4668-4676, 2017 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-28418251

RESUMO

A high-yield, highly diastereo- and enantioselective nitro-Mannich reaction of α-aryl nitromethanes with amidosulfones catalyzed by a novel chiral phase-transfer catalyst, bearing multiple H-bonding donors, derived from quinine was developed. A variety of α-aryl nitromethanes and amidosulfones were investigated; and the corresponding products were obtained in excellent yields with excellent diastereo- and enantioselectivities (up to 99% yield, > 99:1 dr and >99% ee). As a demonstration of synthetic utility, the resulting ß-nitroamines could be converted to corresponding meso-symmetric and optically pure unsymmetric anti-1,2-diarylethylenediamines.

19.
Biochim Biophys Acta Gen Subj ; 1861(7): 1788-1800, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28341484

RESUMO

BACKGROUND: The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression. METHODS: The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR. Co-localization and interaction of RUVBL1 and ITFG1 were determined by immunofluorescence and co-immunoprecipitation. The invasive ability was examined by transwell assay and microfluidic assay. The metastatic and tumorigenic abilities of breast cancer cells were revealed in BALB/c nude mice by xenograft and tail vein injection. RESULTS: ATPase RUVBL1 is highly expressed in breast cancer and predicts the poor prognosis. Elevated expression of RUVBL1 is found in high metastatic breast cancer cells. Silencing RUVBL1 suppresses cancer cell expansion and invasion in vitro and in vivo. RUVBL1 interacts with a conserved transmembrane protein ITFG1 in cytoplasm and plasma membrane to promote the collective invasion. Using a microfluidic model, we demonstrated that silencing RUVBL1 or ITFG1 individually compromises collective invasion of breast cancer cells. CONCLUSION: RUVBL1 is a vital regulator for collective invasion. The interaction between RUVBL1 and ITFG1 is required for breast cancer cell collective invasion and progression. GENERAL SIGNIFICANCE: Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.


Assuntos
Neoplasias da Mama/patologia , Proteínas de Transporte/fisiologia , DNA Helicases/fisiologia , Proteínas de Membrana/fisiologia , ATPases Associadas a Diversas Atividades Celulares , Animais , Proteínas de Transporte/análise , Linhagem Celular Tumoral , DNA Helicases/análise , Transição Epitelial-Mesenquimal , Feminino , Humanos , Proteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Metástase Neoplásica , Ligação Proteica
20.
J Org Chem ; 81(23): 11950-11955, 2016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27802591

RESUMO

We have developed a new base-promoted intermolecular cascade cyclization reaction of substituted 3-aryl(heteroaryl)-3-chloroacrylaldehydes and tetrahydroisoquinolines in one pot. The reaction provides a facile and practical synthesis of pyrrolo[2,1-a]isoquinolines. A number of pyrrolo[2,1-a]isoquinolines were synthesized in moderate to high yields (up to 97%).

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