TY - JOUR
T1 - Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells
AU - Lee, Yeonju
AU - Koay, Eugene J.
AU - Zhang, Weijia
AU - Qin, Lidong
AU - Kirui, Dickson K.
AU - Hussain, Fazle
AU - Shen, Haifa
AU - Ferrari, Mauro
N1 - Funding Information:
The authors gratefully acknowledge funding support from the following sources: Department of Defense grants W81XWH-09-1-0212 and W81XWH-12-1-0414, National Institute of Health grants U54CA143837 and U54CA151668, the CPRIT grant RP121071 from the State of Texas, and the Ernest Cockrell Jr. Distinguished Endowed Chair.
Publisher Copyright:
© 2014 Lee et al.
PY - 2014/10/14
Y1 - 2014/10/14
N2 - We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1), a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM) and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT) markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated Ncadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT). Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.
AB - We report cell mechanical changes in response to alteration of expression of the human equilibrative nucleoside transporter-1 (hENT1), a most abundant and widely distributed plasma membrane nucleoside transporter in human cells and/or tissues. Modulation of hENT1 expression level altered the stiffness of pancreatic cancer Capan-1 and Panc 03.27 cells, which was analyzed by atomic force microscopy (AFM) and correlated to microfluidic platform. The hENT1 knockdown induced reduction of cellular stiffness in both of cells up to 70%. In addition, cellular phenotypic changes such as cell morphology, migration, and expression level of epithelial-mesenchymal transition (EMT) markers were observed after hENT1 knockdown. Cells with suppressed hENT1 became elongated, migrated faster, and had reduced E-cadherin and elevated Ncadherin compared to parental cells which are consistent with epithelial-mesenchymal transition (EMT). Those cellular phenotypic changes closely correlated with changes in cellular stiffness. This study suggests that hENT1 expression level affects cellular phenotype and cell elastic behavior can be a physical biomarker for quantify hENT1 expression and detect phenotypic shift. Furthermore, cell mechanics can be a critical tool in detecting disease progression and response to therapy.
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U2 - 10.1371/journal.pone.0107973
DO - 10.1371/journal.pone.0107973
M3 - Article
C2 - 25314577
AN - SCOPUS:84908096842
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e107973
ER -