title: Human equilibrative nucleoside transporter-1 knockdown tunes cellular mechanics through epithelial-mesenchymal transition in pancreatic cancer cells.
abstract: 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 N-cadherin 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.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America; Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Koay
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Lidong
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Dickson K
authors.initials: DK
authors.lastname: Kirui
authors.affiliation: Department of Mechanical Engineering, Texas Tech University, Lubbock, Texas, United States of America.
authors.forename: Fazle
authors.initials: F
authors.lastname: Hussain
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America; Department of Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002469:Cell Separation; D048429:Cell Size; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D033721:Equilibrative Nucleoside Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D046210:Microfluidic Analytical Techniques; D018625:Microscopy, Atomic Force; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D015820:Cadherins; D033721:Equilibrative Nucleoside Transporter 1; D034741:RNA, Small Interfering; C438649:SLC29A1 protein, human