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中国神经科学学会第十二届全国学术会议

作者： Xu Bo Duan Lu Ye Qin Kai Gao Jiang Shan Zhan Albert Cheung Hoi Yu Lina Li Laboratory For Functional study of astrocytes Neuroscience Research Institute Key Laboratory for Neuroscience of the Ministry of Education

Cell migration is a determinant factor in processes such as tumor metastasis, immune response and wound healing. It shares a range of molecular components with endocytosis such as proteins, and also requires cytoskeleton to be involved as in endocytosis. Up to now, there is not enough information to elucidate the underlying mechanisms how actin structures act synergistically with these components in such processes. Here we report that macropinocytosis, a form of cell drinking, can be induced by physical injury and occurs at the site of ruffling membrane in astrocytes which eventually leads an extra rate of cell migration. The unraveled mechanism was a complex multiple signaling pathway, including calcium, PI3 K, Raf-1, JNK and p38, all of which could modulate macropinocytosis in astrocytes. In addition, for the first time, Raf-1 was determined to be a direct regulator of macropinocytosis via the binding with *** interestingly, such mechanism was also evidenced in other type of cells. We propose here a general mechanism that macropinocytosis is an important cellular response to injury;cell migration could be modified through controlling the occurrence of macropinocytosis under physical injury. A novel and important therapeutic target for modulating cell migration related processes such as wound healing and metastasis might be provided.

关键词： cell migration macropinocytosis injury multiple signaling pathway

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macropinocytosis associated with cell process migration in reactive astrocytes

Macropinocytosis associated with cell process migration in r...

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中国神经科学学会第六届学术会议暨学会成立十周年庆祝大会

作者： Albert Cheung-hoi Yu Neuroscience Research Institute Peking University

＜正＞Reactive astrocyte migration plays a critical role in wound healing and scar formation in many pathological processes. What are the driving force and the molecular mechanism for astrocytes migration is poorly understood. Here we reported a real time visualization of endocytosis in reactive astrocytes induced by scratch injury, and revealed the endocytosis was macropinocytosis. By scanning and transmission electron microscopy, we captured the formation of macropinocytosis from membrane ruffles.

关键词： astrocytes scratch macropinocytosis migration

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NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-Tang Ma Jing-Ping Yun Judy Wai Ping Yam Department of Pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key Laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key Laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of Pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for Comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

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Drug resistance and combating drug resistance in cancer

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Cancer Drug Resistance 2019年第2期2卷 141-160页

作者： Xuan Wang Haiyun Zhang Xiaozhuo Chen Department of Biological Sciences Ohio UniversityAthensOH 45701USA Interdisciplinary Graduate Program in Molecular and Cellular Biology Ohio UniversityAthensOH 45701USA The Edison Biotechnology Institute Ohio UniversityAthensOH 45701USA Department of Chemistry and Biochemistry Ohio UniversityAthensOH 45701USA Department of Biomedical Sciences Heritage College of OsteopathicOhio UniversityAthensOH 45701USA.

Cancer is the second leading cause of death in the *** major treatments for cancer management include surgery,cytotoxic chemotherapy,targeted therapy,radiation therapy,endocrine therapy and *** the endeavors and achievements made in treating cancers during the past decades,resistance to classical chemotherapeutic agents and/or novel targeted drugs continues to be a major problem in cancer *** resistance,either existing before treatment(intrinsic)or generated after therapy(acquired),is responsible for most relapses of cancer,one of the major causes of death of the *** among patients and tumors,and the versatility of cancer to circumvent therapies make drug resistance more challenging to deal *** understanding the mechanisms of drug resistance is required to provide guidance to future cancer treatment and achieve better *** this review,intrinsic and acquired resistance will be *** addition,new discoveries in mechanisms of drug resistance will be ***,we will highlight roles of ATP in drug resistance by discussing recent findings of exceptionally high levels of intratumoral extracellular ATP as well as intracellular ATP internalized from extracellular *** complexity of drug resistance development suggests that combinational and personalized therapies,which should take ATP into consideration,might provide better strategies and improved efficacy for fighting drug resistance in cancer.

关键词： Cancer stem cells epithelial mesenchymal transition ATP binding cassette transporters extracellular ATP macropinocytosis epigenetics microRNA

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Cancer stem cells,epithelial-mesenchymal transition,ATP and their roles in drug resistance in cancer

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Cancer Drug Resistance 2021年第3期4卷 684-709页

作者： Haiyun Zhang Alexander Steed Milo Co Xiaozhuo Chen Department of Biological Science Ohio UniversityAthensOH 45701USA Edison Biotechnology Institute Ohio UniversityAthensOH 45701USA Interdisciplinary Graduate Program in Molecular and Cellular Biology Ohio UniversityAthensOH 45701USA Heritage College of Osteopathic Medicine Ohio UniversityAthensOH 45701USA Department of Biomedical Sciences Ohio UniversityAthensOH 45701USA.

The cancer stem cell(CSC)state and epithelial-mesenchymal transition(EMT)activation are tightly *** cells that acquire the EMT/CSC phenotype are equipped with adaptive metabolic changes to maintain low reactive oxygen species levels and stemness,enhanced drug transporters,anti-apoptotic machinery and DNA repair *** present in the tumor microenvironment such as hypoxia and the communication with non-cancer stromal cells also promote cancer cells to enter the EMT/CSC state and display related ***,particularly the high levels of intratumoral extracellular ATP functioning through both signaling pathways and ATP internalization,induces and regulates EMT and *** three of them work together to enhance drug *** findings in each of these factors will help us explore deeper into mechanisms of drug resistance and suggest new resistance-associated markers and therapeutic targets.

关键词： Tumor microenvironment macropinocytosis ATP internalization ABC transporters biological markers apoptosis

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Entry of Bombyx mori nucleopolyhedroviruse（Bm NPV） into BmN Cells by cholesterol-dependent macropinocytic endocytosis

Entry of Bombyx mori nucleopolyhedroviruse（Bm NPV） into Bm...

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中国蚕学会第八届青年学术研讨会

作者： Jinshan Huang Bifang Hao Xingjia Shen Chen Cheng Fei Liang Shengpeng Wang College of Biotechnology Jiangsu University of Science and Technology Sericultural Research Institute Chinese Academy of Agricultural Science

BmNPV is a serious viral pathogen of silkworm, and no drug or specific protection is available at present time. Although most genes’ function of BmNPV was depicted in recent years, knowledge on BmNPV entry into cells is still limited. Here BmNPV cell entry mechanism is investigated by different endocytic inhibitor application and subcellular analysis. Results indicated that BmNPV enters BmN cells by clathrin-indepedent macropinocytic endocytosis, which is mediated by cholesterol in a dose dependent manner, and cholesterol replenishment rescued the BmNPV infection partially.

关键词： BmNPV macropinocytosis Endocytosis Cholesterol

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How do alpha-Coronaviruses take advantage of host's sources to establish their infection

How do alpha-Coronaviruses take advantage of host's sources ...

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第十二届全国免疫学学术大会

作者： wang yu-e Luo Xiaolei Guo Longjun Harbin Veterinary Research Institute

We found that alpha-coronavirus PEDV infection of epithelial cells results in disruption of the tight junctional distribution of occludin to its intracellular *** of occludin in target cells makes them more susceptible to PEDV infection,whereas ablation of occludin expression by use of small interfering RNA(siRNA) in target cells significantly reduces their susceptibility to virus ***,we observed that macropinocytosis inhibitors blocked occludin internalization and virus entry,indicating that virus entry and occludin internalization are closely ***,the macropinocytosis inhibitors could not impede virus replication once the virus had entered host *** suggests that occludin internalization by a macropinocytosis-like process is involved in the virus entry *** microscopy showed that PEDV was trapped at cellular junctional regions upon macropinocytosis inhibitor treatment,indicating that occludin may serve as a scaffold in the vicinity of virus *** same time,we observed that this virus was relatively resistant to treatment with type Ⅰ *** blot analysis showed that STAT1 expression was markedly reduced in PEDV-infected cells and that this reduction was not due to inhibition of STAT1 ***1 downregulation was blocked by a proteasome inhibitor but not by an autophagy inhibitor,strongly implicating the ubiquitin-proteasome targeting degradation *** PEDV infection-induced STAT1 degradation was evident in cells pretreated with the general tyrosine kinase inhibitor,we conclude that STAT1 degradation is independent of the IFN signaling ***,we report that PEDV-induced STAT1 degradation inhibits IFN-alpha signal transduction *** inhibition of STAT1 degradation rescued the ability of the host to suppress virus ***,to establish PEDV infection,coronavirus utilize occludin as a scaffold to entry into cells;virus can further s

关键词： alpha-coronavirus occludin macropinocytosis STAT1

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Preparation and Characterization of Teniposide PLGA Nanoparticles and Their Uptake in Human Glioblastoma U87MG Cells

Preparation and Characterization of Teniposide PLGA Nanopart...

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2013年广东省药师周大会

作者： Liqian Mo Lianbing Hou Dan Guo Xiaoyan Xiao Ping Mao Xixiao Yang Department ofPharmacy Nanfang HospitalSouthern Medical University

Many studies have demonstrated the uptake mechanisms of various nanoparticle delivery systems with different physicochemical properties in different *** this study,we report for the first time the preparation and characterization of teniposide(VM-26) poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles(NPs) and their cellular uptake pathways in human glioblastoma U87MG *** nanoparticles prepared with oil-in-water(O/W) single-emulsion solvent evaporation method had a small particle size and spherical shape and provided effective protection against degradation of teniposide in PBS *** scanning calorimetry(DSC) thermograms concluded that VM-26 was dispersed as amorphous or disordered crystalline phase in the PLGA matrix.A cytotoxicity study revealed that,in a 24 hour period,blank PLGA NPs had no cytotoxicity,whereas teniposide-loaded PLGA NPs(VM-26-NPs)had U87MG cytotoxicity levels similar to free *** laser scanning microscopy(CLSM) and transmission electron microscopy(TEM) images showed the distribution and degradation processes of nanoparticles in *** endocytosis inhibition test indicated that clathrin-mediated endocytosis and macropinocytosis were the primary modes of engulfment involved in the internalization of *** findings suggest that PLGA nanoparticles containing a sustained release formula of teniposide may multiplex the therapeutic effect and ultimately degrade in lysosomal within human glioblastoma U87MG cells.

关键词： Teniposide PLGA Nanoparticle Endocytosis Clathrin macropinocytosis

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