26 results on '"Chu, Yeh-Shiu"'
Search Results
2. Dual targeted extracellular vesicles regulate oncogenic genes in advanced pancreatic cancer
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Chiang, Chi-Ling, Ma, Yifan, Hou, Ya-Chin, Pan, Junjie, Chen, Sin-Yu, Chien, Ming-Hsien, Zhang, Zhi-Xuan, Hsu, Wei-Hsiang, Wang, Xinyu, Zhang, Jingjing, Li, Hong, Sun, Lili, Fallen, Shannon, Lee, Inyoul, Chen, Xing-Yu, Chu, Yeh-Shiu, Zhang, Chi, Cheng, Tai-Shan, Jiang, Wen, Kim, Betty Y. S., Reategui, Eduardo, Lee, Robert, Yuan, Yuan, Liu, Hsiao-Chun, Wang, Kai, Hsiao, Michael, Huang, Chi-Ying F., Shan, Yan-Shen, Lee, Andrew S., and James Lee, L.
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- 2023
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3. Secretory autophagy promotes Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1
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Wu, Shan-Ying, Chen, Jia-Wen, Liu, Hsi-Yu, Wang, Yi-Ching, Chu, Yeh-Shiu, Huang, Chi-Ying, Lan, Kai-Ying, Liu, Hsiao-Sheng, and Lan, Sheng-Hui
- Published
- 2022
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4. Elevation of Intra-Cellular Calcium in Nucleus Pulposus Cells with Micro-Pipette-Guided Ultrasound
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Chu, Ya-Cherng, Lim, Jormay, Lai, Chien-Hsi, Tseng, Mu-Cyun, Chu, Yeh-Shiu, and Wang, Jaw-Lin
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- 2021
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5. Force Measurements in E-Cadherin-Mediated Cell Doublets Reveal Rapid Adhesion Strengthened by Actin Cytoskeleton Remodeling through Rac and Cdc42
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Chu, Yeh-Shiu, Thomas, William A., Eder, Olivier, Pincet, Frederic, Perez, Eric, Thiery, Jean Paul, and Dufour, Sylvie
- Published
- 2004
6. Extracellular domains of E-cadherin determine key mechanical phenotypes of an epithelium through cell- and non-cell-autonomous outside-in signaling.
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Aladin, Darwesh Mohideen Kaderbatcha, Chu, Yeh Shiu, Shen, Shuo, Robinson, Robert Charles, Dufour, Sylvie, Viasnoff, Virgile, Borghi, Nicolas, and Thiery, Jean Paul
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CELL adhesion , *CADHERINS , *CELLULAR mechanics , *CELL migration , *CELL cycle proteins , *EPITHELIUM - Abstract
Cadherins control intercellular adhesion in most metazoans. In vertebrates, intercellular adhesion differs considerably between cadherins of type-I and type-II, predominantly due to their different extracellular regions. Yet, intercellular adhesion critically depends on actomyosin contractility, in which the role of the cadherin extracellular region is unclear. Here, we dissect the roles of the Extracellular Cadherin (EC) Ig-like domains by expressing chimeric E-cadherin with E-cadherin and cadherin-7 Ig-like domains in cells naturally devoid of cadherins. Using cell-cell separation, cortical tension measurement, tissue stretching and migration assays, we show that distinct EC repeats in the extracellular region of cadherins differentially modulate epithelial sheet integrity, cell-cell separation forces, and cell cortical tension with the Cdc42 pathway, which further differentially regulate epithelial tensile strength, ductility, and ultimately collective migration. Interestingly, dissipative processes rather than static adhesion energy mostly dominate cell-cell separation forces. We provide a framework for the emergence of epithelial phenotypes from cell mechanical properties dependent on EC outside-in signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. Effects of electrode diameter on the detection sensitivity and frequency characteristics of electric cell-substrate impedance sensing.
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Lai, Yi-Ting, Chu, Yeh-Shiu, Lo, Jun-Chih, Hung, Yu-Han, and Lo, Chun-Min
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ELECTRIC impedance , *ELECTRODES , *DIAMETER , *IMPEDANCE spectroscopy , *CELL migration , *BIRD migration - Abstract
Highlights • We investigated four different cell lines cultured on sensing electrodes with four different diameters, 25, 50, 100, and 250 μm. • As sensing electrode diameter decreases, the optimal detection sensitivity decreases and the optimal detection frequency increases. • 250 μm is approximately the optimal electrode diameter for ECIS measurement. • We applied these criteria to sensitively detect dynamic responses of MDA-MB-231 cells to TGF-β1. • The transient increase of measured impedance after TGF-β1 treatment coincided with the increased cell migration rate. Abstract Cell-based electrochemical impedance spectroscopy (EIS) has emerged as a label-free approach to monitor whole cellular behavior in response to the environmental stimuli in real time. The measured impedance is strongly dependent on the attached cells, the sensing electrode size, and the constriction resistance between the sensing electrode and its counter electrode. However, determining the optimal electrode size for sensitive detection of impedance characteristics of the attached cells remains a challenge. In this study, four different cell lines (MDCK, MCF-7, HUVEC, and MDA-MB-231 cells) were cultured on the sensing electrodes with four different diameters, 250, 100, 50, and 25 μm, and impedance measurements were performed at frequencies ranging from 25 Hz to 64 kHz using electric cell-substrate impedance sensing (ECIS) method. As the diameter of sensing electrode decreases, the peak value (optimal detection sensitivity) of the normalized resistance spectrum decreases and the peak position (optimal detection frequency) shifts to the high-frequency region. These criteria were applied to sensitively measure impedance changes of MDA-MB-231 cells in response to TGF-β1 treatment. The transient increase of measured impedance after TGF-β1 treatment coincided with the augmented formation of the peripheral paxillin-rich sites and the increased cell migration rate, while little difference in cell spreading area was observed. Our results suggest that 250 μm is approximately the optimal electrode diameter for EIS measurement if sensitively monitoring the morphological changes of adherent cells is required. [ABSTRACT FROM AUTHOR]
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- 2019
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8. Design of an ultrasound chamber for cellular excitation and observation.
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Chu, Ya-Cherng, Lim, Jormay, Hong, Cheng-Wei, Chu, Yeh-Shiu, and Wang, Jaw-Lin
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ULTRASONIC imaging ,LAMB waves ,MAMMARY glands ,CELL imaging ,EPITHELIAL cells - Abstract
In this work, a design of integrating ultrasonic transduction with live cell imaging chamber is introduced. The principle of a metal-incident-glass-output acoustic path was used to deliver a uniform energy profile into the imaging/incubation chamber in the form of leaky Lamb waves. The design was applied to examine living mouse mammary gland epithelial cells (EpH4). Significant changes in intracellular activities were observed even at a very low energy intensity level (1 MHz, I
SATA = 1 mW/cm2 , continuous wave). Live imaging with ultrasonic stimulation provides a different paradigm to interrogate cellular mechanosensitive responses in real time. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Videography supported adhesion, and proliferation behavior of MG-63 osteoblastic cells on 2.5D titania nanotube matrices.
- Author
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Manurung, Robeth Viktoria, Fu, Pei‐Wen, Chu, Yeh‐Shiu, Lo, Chun‐Min, and Chattopadhyay, Surojit
- Abstract
Human osteosarcoma cells MG-63 were cultured on anodically etched titania nanotubes (TiO
2 NT), with diameters ranging from 40-100 nm, to study the correlations between cell proliferation and adhesion on the 2.5 dimensional (2.5D) extracellular matrix (ECM). Unlike other reports, mostly based on mouse stem cells, and 2D cell culture, our studies indicate that the 2.5D NT promote higher proliferation and activity, but less 2D adhesion. Proliferation of the MG-63 cells was significantly higher in the NTs, the best being the 70 nm diameter sample, compared to planar titania (control). This is consistent with previous studies. However, cellular adhesion was stronger on TiO2 NT with increasing diameter, and highest on the control as obtained from shear stress measurement, paxilin imaging, and western blot measurements probing focal adhesion kinase, p130 CAS, and extracellular-regulated kinase, in addition to cell morphology imaging by fluorescence microscopy. We provide direct videography of cell migration, and cell speed data indicating faster filopodial activity on the TiO2 NT surfaces having lower adhesion. This evidence was not available previously. The NT matrices promote cells with smaller surface area, because of less 2D stretching. In contrast, on comparatively planar 2D-like surfaces uniaxial stretching of the cell body with strong anchoring of the filopodia, resulted in larger cell surface area, and demonstrated stronger adhesion. The difference in the results, with those previously published, may be generally attributed to, among others, the use of mouse stem cells (human osteosarcoma used here), and unannealed as-grown TiO2 NTs used previously (annealed ECMs used here). © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 842-852, 2016. [ABSTRACT FROM AUTHOR]- Published
- 2016
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10. EMT-Induced Stemness and Tumorigenicity Are Fueled by the EGFR/Ras Pathway.
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Voon, Dominic Chih-Cheng, Wang, Huajing, Koo, Jason Kin Wai, Chai, Juin Hsien, Hor, Yit Teng, Tan, Tuan Zea, Chu, Yeh-Shiu, Mori, Seiichi, and Ito, Yoshiaki
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EPIDERMAL growth factor receptors ,EPITHELIAL cells ,CELL differentiation ,NEOPLASTIC cell transformation ,GENE expression ,BIOLOGICAL assay ,PLASTIC foams - Abstract
Recent studies have revealed that differentiated epithelial cells would acquire stem cell-like and tumorigenic properties following an Epithelial-Mesenchymal Transition (EMT). However, the signaling pathways that participate in this novel mechanism of tumorigenesis have not been fully characterized. In Runx3
−/− p53−/− murine gastric epithelial (GIF-14) cells, EMT-induced plasticity is reflected in the expression of the embryonal proto-oncogene Hmga2 and Lgr5, an exclusive gastrointestinal stem cell marker. Here, we report the concurrent activation of an EGFR/Ras gene expression signature during TGF-β1-induced EMT in GIF-14 cells. Amongst the altered genes was the induction of Egfr, which corresponded with a delayed sensitization to EGF treatment in GIF-14. Co-treatment with TGF-β1 and EGF or the expression of exogenous KRas led to increased Hmga2 or Lgr5 expression, sphere initiation and colony formation in soft agar assay. Interestingly, the gain in cellular plasticity/tumorigenicity was not accompanied by increased EMT. This uncoupling of EMT and the induction of plasticity reveals an involvement of distinct signaling cues, whereby the EGFR/Ras pathway specifically promotes stemness and tumorigenicity in EMT-altered GIF-14 cells. These data show that the EGFR/Ras pathway requisite for the sustenance of gastric stem cells in vivo and in vitro is involved in the genesis and promotion of EMT-induced tumor-initiating cells. [ABSTRACT FROM AUTHOR]- Published
- 2013
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11. Runx3 Protects Gastric Epithelial Cells Against Epithelial-Mesenchymal Transition-Induced Cellular Plasticity and Tumorigenicity.
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Voon, Dominic Chih-Cheng, Wang, Huajing, Koo, Jason Kin Wai, Nguyen, Tu Anh Pham, Hor, Yit Teng, Chu, Yeh-Shiu, Ito, Kosei, Fukamachi, Hiroshi, Chan, Shing Leng, Thiery, Jean Paul, and Ito, Yoshiaki
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RUNX proteins ,STOMACH cancer ,CANCER stem cells ,TRANSFORMING growth factors ,TRANSCRIPTION factors ,TUMOR suppressor proteins ,CARCINOGENESIS - Abstract
The transcription factor RUNX3 functions as a tumor suppressor in the gastrointestinal epithelium, where its loss is an early event in carcinogenesis. While RUNX3 acts concurrently as a mediator of TGF-β signaling and an antagonist of Wnt, the cellular changes that follow its loss and their contribution to tumorigenicity are not fully understood. Here, we report that the loss of Runx3 in gastric epithelial cells results in spontaneous epithelial-mesenchymal transition (EMT). This produces a tumorigenic stem cell-like subpopulation, which remarkably expresses the gastric stem cell marker Lgr5. This phenomenon is due to the compounding effects of the dysregulation of the TGF-β and Wnt pathways. Specifically, Runx3
−/− p53−/− gastric epithelial cells were unexpectedly sensitized for TGF-β-induced EMT, during which the resultant induction of Lgr5 was enhanced by an aberrantly activated Wnt pathway. These data demonstrate a protective role for RUNX3 in safeguarding gastric epithelial cells against aberrant growth factor signaling and the resultant cellular plasticity and stemness. S TEM C ells 2012;30:2088-2099 [ABSTRACT FROM AUTHOR]- Published
- 2012
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12. Stimulatory and entraining effect of melatonin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretion.
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Chu, Yeh-Shiu, Shieh, Kun-Ruey, Yuan, Zung Fan, and Pan, Jenn-Tser
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- 2000
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13. Circadian change of dopaminergic neuron activity.
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Shieh, Kun-Ruey, Chu, Yeh-Shiu, and Pan, Jenn-Tser
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- 1997
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14. Glucose Transporter 3 Is Essential for the Survival of Breast Cancer Cells in the Brain.
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Kuo, Min-Hsun, Chang, Wen-Wei, Yeh, Bi-Wen, Chu, Yeh-Shiu, Lee, Yueh-Chun, and Lee, Hsueh-Te
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GLUCOSE transporters ,CREB protein ,CANCER cells ,METASTATIC breast cancer ,BRAIN tumors - Abstract
Breast cancer brain metastasis commonly occurs in one-fourth of breast cancer patients and is associated with poor prognosis. Abnormal glucose metabolism is found to promote cancer metastasis. Moreover, the tumor microenvironment is crucial and plays an active role in the metabolic adaptations and survival of cancer cells. Glucose transporters are overexpressed in cancer cells to increase glucose uptake. The glucose transporter 3 (GLUT3) is a high-affinity glucose transporter that is highly expressed in mammalian neurons. GLUT3 is also overexpressed in several malignant brain tumors. However, the role of GLUT3 in breast cancer brain metastasis remains unknown. The results of the present study demonstrated that GLUT3 is highly overexpressed in brain metastatic breast cancers and mediates glucose metabolic reprogramming. Furthermore, knockdown of cAMP-response element binding protein (CREB) could directly regulate GLUT3 expression in brain metastatic breast cancer cells. Notably, we verified and provided a novel role of GLUT3 in mediating glucose metabolism and assisting breast cancer cells to survive in the brain to promote brain metastasis. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer.
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Hsu, Jade H.-M., Chang, Peter M.-H., Cheng, Tai-Shan, Kuo, Yu-Lun, Wu, Alexander T.-H., Tran, Thu-Ha, Yang, Yun-Hsuan, Chen, Jing-Ming, Tsai, Yu-Chen, Chu, Yeh-Shiu, Huang, Tse- Hung, Huang, Chi-Ying F., and Lai, Jin-Mei
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AUTOPHAGY ,REACTIVE oxygen species ,ANIMAL experimentation ,APOPTOSIS ,CANCER chemotherapy ,CARRIER proteins ,CELL lines ,CELLULAR signal transduction ,COMBINATION drug therapy ,CISPLATIN ,DRUG resistance in cancer cells ,CLINICAL drug trials ,EPIDERMAL growth factor ,LUNG cancer ,MEDICINAL plants ,MICE ,PROTEIN kinases ,PROTEINS ,STEROIDS ,PLANT extracts ,CELL survival ,PEMETREXED ,IN vivo studies ,PHARMACODYNAMICS - Abstract
Low response rate and recurrence are common issues in lung cancer; thus, identifying a potential compound for these patients is essential. Utilizing an in silico screening method, we identified withaferin A (WA), a cell-permeable steroidal lactone initially extracted from Withania somnifera, as a potential anti–lung cancer and anti–lung cancer stem-like cell (CSC) agent. First, we demonstrated that WA exhibited potent cytotoxicity in several lung cancer cells, as evidenced by low IC
50 values. WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects. The increase in p62 indicated that WA may modulate the autophagy flux followed by apoptosis. In vivo research also demonstrated the anti-tumor effect of WA treatment. We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity, at least through downregulation of mTOR/STAT3 signaling. Furthermore, the combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability. In addition, WA can further enhance the cytotoxic effect of cisplatin in lung CSCs. Therefore, WA alone or in combination with standard chemotherapy is a potential treatment option for EGFR wild-type lung cancer and may decrease the occurrence of cisplatin resistance by inhibiting lung CSCs. [ABSTRACT FROM AUTHOR]- Published
- 2019
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16. The Universal Dynamics of Cell Spreading
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Cuvelier, Damien, Théry, Manuel, Chu, Yeh-Shiu, Dufour, Sylvie, Thiéry, Jean-Paul, Bornens, Michel, Nassoy, Pierre, and Mahadevan, L.
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CELL adhesion , *CELL communication , *CONNECTIVE tissues , *CELLS - Abstract
Summary: Cell adhesion and motility depend strongly on the interactions between cells and extracellular matrix (ECM) substrates. When plated onto artificial adhesive surfaces, cells first flatten and deform extensively as they spread. At the molecular level, the interaction of membrane-based integrins with the ECM has been shown to initiate a complex cascade of signaling events , which subsequently triggers cellular morphological changes and results in the generation of contractile forces . Here, we focus on the early stages of cell spreading and probe their dynamics by quantitative visualization and biochemical manipulation with a variety of cell types and adhesive surfaces, adhesion receptors, and cytoskeleton-altering drugs. We find that the dynamics of adhesion follows a universal power-law behavior. This is in sharp contrast with the common belief that spreading is regulated by either the diffusion of adhesion receptors toward the growing adhesive patch or by actin polymerization . To explain this, we propose a simple quantitative and predictive theory that models cells as viscous adhesive cortical shells enclosing a less viscous interior. Thus, although cell spreading is driven by well-identified biomolecular interactions, it is dynamically limited by its mesoscopic structure and material properties. [Copyright &y& Elsevier]
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- 2007
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17. The first World Cell Race
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Maiuri, Paolo, Terriac, Emmanuel, Paul-Gilloteaux, Perrine, Vignaud, Timothée, McNally, Krista, Onuffer, James, Thorn, Kurt, Nguyen, Phuong A., Georgoulia, Nefeli, Soong, Daniel, Jayo, Asier, Beil, Nina, Beneke, Jürgen, Lim, Joleen Chooi Hong, Sim, Chloe Pei-Ying, Chu, Yeh-Shiu, Jiménez-Dalmaroni, Andrea, Joanny, Jean-François, Thiery, Jean-Paul, and Erfle, Holger
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- 2013
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18. The first World Cell Race
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Maiuri, Paolo, Terriac, Emmanuel, Paul-Gilloteaux, Perrine, Vignaud, Timothée, McNally, Krista, Onuffer, James, Thorn, Kurt, Nguyen, Phuong A., Georgoulia, Nefeli, Soong, Daniel, Jayo, Asier, Beil, Nina, Beneke, Jürgen, Hong Lim, Joleen Chooi, Pei-Ying Sim, Chloe, Chu, Yeh-Shiu, Jiménez-Dalmaroni, Andrea, Joanny, Jean-François, Thiery, Jean-Paul, and Erfle, Holger
- Subjects
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CELL motility , *COLLAGEN , *MORPHOGENESIS , *IMMUNE response , *CANCER cells , *METASTASIS , *CELL migration - Abstract
Summary: Motility is a common property of animal cells. Cell motility is required for embryogenesis [1], tissue morphogenesis [2] and the immune response [3] but is also involved in disease processes, such as metastasis of cancer cells [4]. Analysis of cell migration in native tissue in vivo has yet to be fully explored, but motility can be relatively easily studied in vitro in isolated cells. Recent evidence suggests that cells plated in vitro on thin lines of adhesive proteins printed onto culture dishes can recapitulate many features of in vivo migration on collagen fibers [5,6]. However, even with controlled in vitro measurements, the characteristics of motility are diverse and are dependent on the cell type, origin and external cues. One objective of the first World Cell Race was to perform a large-scale comparison of motility across many different adherent cell types under standardized conditions. To achieve a diverse selection, we enlisted the help of many international laboratories, who submitted cells for analysis. The large-scale analysis, made feasible by this competition-oriented collaboration, demonstrated that higher cell speed correlates with the persistence of movement in the same direction irrespective of cell origin. [ABSTRACT FROM AUTHOR]
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- 2012
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19. Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.
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Li H, Chiang CL, Kwak KJ, Wang X, Doddi S, Ramanathan LV, Cho SM, Hou YC, Cheng TS, Mo X, Chang YS, Chang HL, Cheng W, Tsai WN, Nguyen LTH, Pan J, Ma Y, Rima XY, Zhang J, Reategui E, Chu YS, Chang PM, Chang PH, Huang CF, Wang CH, Shan YS, Li CP, Fleisher M, and Lee LJ
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- Humans, Biomarkers, Tumor genetics, Glypicans genetics, Glypicans metabolism, Prognosis, RNA, Messenger genetics, RNA, Messenger metabolism, Carcinoma, Pancreatic Ductal diagnosis, Carcinoma, Pancreatic Ductal genetics, Extracellular Vesicles metabolism, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms genetics
- Abstract
Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
- Published
- 2024
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20. Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors.
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Chen SW, Hung YS, Fuh JL, Chen NJ, Chu YS, Chen SC, Fann MJ, and Wong YH
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- Adenosine Diphosphate pharmacology, Adenosine Triphosphate pharmacology, Biomarkers metabolism, Calcium Signaling drug effects, Cell Movement drug effects, Culture Media pharmacology, Gene Expression Profiling, Gene Expression Regulation drug effects, Humans, Induced Pluripotent Stem Cells drug effects, Induced Pluripotent Stem Cells metabolism, Microglia drug effects, Cell Differentiation drug effects, Cell Differentiation genetics, Induced Pluripotent Stem Cells cytology, Microglia cytology, Transcription Factors metabolism
- Abstract
Microglia, the immune cells of the central nervous system, play critical roles in brain physiology and pathology. We report a novel approach that produces, within 10 days, the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. High-level expression of the main microglial markers and the purity of the iMG cells were confirmed by RT-qPCR, immunostaining, and flow cytometry analyses. Whole-transcriptome analysis demonstrated that these iMGs resemble human fetal/adult microglia but not human monocytes. Moreover, these iMGs exhibited appropriate physiological functions, including various inflammatory responses, ADP/ATP-evoked migration, and phagocytic ability. When co-cultured with hiPSC-derived neurons, the iMGs respond and migrate toward injured neurons. This study has established a protocol for the rapid conversion of hiPSCs into functional iMGs, which should facilitate functional studies of human microglia using different disease models and also help with drug discovery., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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21. Low Intensity Ultrasound Induces Epithelial Cell Adhesion Responses.
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Lim J, Chu YS, Chu YC, Lo CM, and Wang JL
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- Animals, Mice, Phosphorylation, Crk-Associated Substrate Protein metabolism, Cadherins metabolism, Epithelial Cells metabolism, Epithelial Cells radiation effects, Epithelial Cells cytology, Ultrasonic Waves, Cell Adhesion
- Abstract
In this study, we investigated the cellular mechanosensitive responses to a low intensity ultrasound (LIUS) stimulation (ISATA = 1 mW/cm2, pressure = 10 kPa). The dose and temporal effects at cell-substrate adhesion (CSA) at the basal level and cell-cell adhesion (CCA) at the apical level are reported in detail. A model of mouse mammary gland epithelial cells (EpH4) and the phosphorylation of mechanosensitive 130 kDa Crk-associated substrate (p130CAS) as an indicator for cellular responses were used. The intensity of phospho-p130CAS was found to be dependent on LIUS stress level, and the p130CAS was phosphorylated after 1 min stimulation at CSA. The phospho-p130CAS was also found to increase significantly at CCA upon LIUS stimulation. We confirmed that the cellular responses to ultrasound are immediate and dose dependent. Ultrasound affects not only CSA but also CCA. An E-cadherin knockout (EpH4ECad-/-) model also confirmed that phosphorylation of p130CAS at CCA is related to E-cadherins., (Copyright © 2020 by ASME.)
- Published
- 2020
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22. High-Affinity Ligands Can Trigger T Cell Receptor Signaling Without CD45 Segregation.
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Al-Aghbar MA, Chu YS, Chen BM, and Roffler SR
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- Animals, CD3 Complex antagonists & inhibitors, Calcium metabolism, Cell Line, Tumor, Disease Models, Animal, Humans, Ligands, Lipid Bilayers chemistry, Lipid Bilayers metabolism, Lymphocyte Activation immunology, Phosphorylation, Protein Binding, Single-Chain Antibodies pharmacology, ZAP-70 Protein-Tyrosine Kinase metabolism, Leukocyte Common Antigens metabolism, Receptors, Antigen, T-Cell metabolism, Signal Transduction, T-Lymphocytes immunology, T-Lymphocytes metabolism
- Abstract
How T cell receptors (TCRs) are triggered to start signaling is still not fully understood. It has been proposed that segregation of the large membrane tyrosine phosphatase CD45 from engaged TCRs initiates signaling by favoring phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic domains of CD3 molecules. However, whether CD45 segregation is important to initiate triggering is still uncertain. We examined CD45 segregation from TCRs engaged to anti-CD3 scFv with high or low affinity and with defined molecular lengths on glass-supported lipid bilayers using total internal reflection microscopy. Both short and elongated high-affinity anti-CD3 scFv effectively induced similar calcium mobilization, Zap70 phosphorylation, and cytokine secretion in Jurkat T cells but CD45 segregated from activated TCR microclusters significantly less for elongated versus short anti-CD3 ligands. In addition, at early times, triggering cells with both high and low affinity elongated anti-CD3 scFv resulted in similar degrees of CD3 co-localization with CD45, but only the high-affinity scFv induced T cell activation. The lack of correlation between CD45 segregation and early markers of T cell activation suggests that segregation of CD45 from engaged TCRs is not mandatory for initial triggering of TCR signaling by elongated high-affinity ligands.
- Published
- 2018
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23. Microfluidic cell trap array for controlled positioning of single cells on adhesive micropatterns.
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Lin L, Chu YS, Thiery JP, Lim CT, and Rodriguez I
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- Cell Adhesion, Cells, Cultured, Fibronectins chemistry, HeLa Cells, Humans, Hydrodynamics, Microfluidic Analytical Techniques instrumentation, Microfluidic Analytical Techniques methods
- Abstract
Adhesive micropattern arrays permit the continuous monitoring and systematic study of the behavior of spatially confined cells of well-defined shape and size in ordered configurations. This technique has contributed to defining mechanisms that control cell polarity and cell functions, including proliferation, apoptosis, differentiation and migration in two-dimensional cell culture systems. These micropattern studies often involve isolating a single cell on one adhesive protein micropattern using random seeding methods. Random seeding has been successful for isolated and, to a lesser degree, paired patterns, where two patterns are placed in close proximity. Using this method, we found that the probability of obtaining one cell per pattern decreases significantly as the number of micropatterns in a cluster increases, from 16% for paired micropatterns to 0.3% for clusters of 6 micropatterns. This work presents a simple yet effective platform based on a microfludic sieve-like trap array to exert precise control over the positioning of single cells on micropatterns. We observed a 4-fold improvement over random seeding in the efficiency of placing a pair of single cells on paired micropattern and a 40-fold improvement for 6-pattern clusters. The controlled nature of this platform can also allow the juxtaposition of two different cell populations through a simple modification in the trap arrangement. With excellent control of the identity, number and position of neighbouring cells, this cell-positioning platform provides a unique opportunity for the extension of two-dimensional micropattern studies beyond paired micropatterns to organizations containing many cells or different cell types.
- Published
- 2013
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24. α-Catenin and vinculin cooperate to promote high E-cadherin-based adhesion strength.
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Thomas WA, Boscher C, Chu YS, Cuvelier D, Martinez-Rico C, Seddiki R, Heysch J, Ladoux B, Thiery JP, Mege RM, and Dufour S
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- Actins metabolism, Animals, Cell Adhesion, Cytoskeletal Proteins metabolism, Cytoskeleton metabolism, Gene Deletion, Mice, Microscopy, Fluorescence methods, Models, Biological, Models, Genetic, Mutation, Protein Binding, Time Factors, Cadherins metabolism, Gene Expression Regulation, Vinculin metabolism, alpha Catenin metabolism
- Abstract
Maintaining cell cohesiveness within tissues requires that intercellular adhesions develop sufficient strength to support traction forces applied by myosin motors and by neighboring cells. Cadherins are transmembrane receptors that mediate intercellular adhesion. The cadherin cytoplasmic domain recruits several partners, including catenins and vinculin, at sites of cell-cell adhesion. Our study used force measurements to address the role of αE-catenin and vinculin in the regulation of the strength of E-cadherin-based adhesion. αE-catenin-deficient cells display only weak aggregation and fail to strengthen intercellular adhesion over time, a process rescued by the expression of αE-catenin or chimeric E-cadherin·αE-catenins, including a chimera lacking the αE-catenin dimerization domain. Interestingly, an αE-catenin mutant lacking the modulation and actin-binding domains restores cadherin-dependent cell-cell contacts but cannot strengthen intercellular adhesion. The expression of αE-catenin mutated in its vinculin-binding site is defective in its ability to rescue cadherin-based adhesion strength in cells lacking αE-catenin. Vinculin depletion or the overexpression of the αE-catenin modulation domain strongly decreases E-cadherin-mediated adhesion strength. This supports the notion that both molecules are required for intercellular contact maturation. Furthermore, stretching of cell doublets increases vinculin recruitment and α18 anti-αE-catenin conformational epitope immunostaining at cell-cell contacts. Taken together, our results indicate that αE-catenin and vinculin cooperatively support intercellular adhesion strengthening, probably via a mechanoresponsive link between the E-cadherin·β-catenin complexes and the underlying actin cytoskeleton.
- Published
- 2013
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25. Prototypical type I E-cadherin and type II cadherin-7 mediate very distinct adhesiveness through their extracellular domains.
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Chu YS, Eder O, Thomas WA, Simcha I, Pincet F, Ben-Ze'ev A, Perez E, Thiery JP, and Dufour S
- Subjects
- Animals, Avian Proteins chemistry, Avian Proteins genetics, Cadherins chemistry, Cadherins genetics, Cell Line, Chickens, Intercellular Junctions, Kinetics, Membrane Microdomains physiology, Transfection, beta Catenin genetics, beta Catenin metabolism, Avian Proteins physiology, Cadherins physiology, Cell Adhesion
- Abstract
Using a dual pipette assay that measures the force required to separate adherent cell doublets, we have quantitatively compared intercellular adhesiveness mediated by Type I (E- or N-cadherin) or Type II (cadherin-7 or -11) cadherins. At similar cadherin expression levels, cells expressing Type I cadherins adhered much more rapidly and strongly than cells expressing Type II cadherins. Using chimeric cadherins, we found that the extracellular domain exerts by far the dominant effect on cell adhesivity, that of E-cadherin conferring high adhesivity, and that of cadherin-7 conferring low adhesivity. Type I cadherins were incorporated to a greater extent into detergent-insoluble cytoskeletal complexes, and their cytoplasmic tails were much more effective in disrupting strong adherent junctions, suggesting that Type II cadherins form less stable complexes with beta-catenin. The present study demonstrates compellingly, for the first time, that cadherins are dramatically different in their ability to promote intercellular adhesiveness, a finding that has profound implications for the regulation of tissue morphogenesis.
- Published
- 2006
- Full Text
- View/download PDF
26. Johnson-Kendall-Roberts theory applied to living cells.
- Author
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Chu YS, Dufour S, Thiery JP, Perez E, and Pincet F
- Subjects
- Animals, Cell Line, Tumor, Cell Membrane, Computer Simulation, Elasticity, Mice, Micromanipulation methods, Sarcoma pathology, Stress, Mechanical, Cell Adhesion, Cytoskeleton, Membrane Fluidity, Membrane Fusion, Models, Biological, Sarcoma physiopathology
- Abstract
Johnson-Kendall-Roberts (JKR) theory is an accurate model for strong adhesion energies of soft slightly deformable material. Little is known about the validity of this theory on complex systems such as living cells. We have addressed this problem using a depletion controlled cell adhesion and measured the force necessary to separate the cells with a micropipette technique. We show that the cytoskeleton can provide the cells with a 3D structure that is sufficiently elastic and has a sufficiently low deformability for JKR theory to be valid. When the cytoskeleton is disrupted, JKR theory is no longer applicable.
- Published
- 2005
- Full Text
- View/download PDF
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