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Title:Mechanical and epigenetic regulation of cell plasticity and tumorigenicity
Author(s):Singh, Rishi Bal
Advisor(s):Wang, Ning
Department / Program:Mechanical Science & Engineering
Discipline:Mechanical Engineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:M.S.
Genre:Thesis
Subject(s):Nuclear Protein 1 (Nupr1)
Sox2
tumorigenesis
plasticity
cancer
epigenetics
mechanics
tumor microenvironment
Abstract:Nupr1 is a protein initially identified as a cancer cell marker, though its role in cancer cell metastasis and tumorigenesis is currently ambiguous. Here we identify Nupr1 as a mechanosensitive protein involved in the regulation of tumor cell plasticity and Sox2 expression. We monitored Nupr1 and Sox2 expression over time in cells cultured in soft 3D fibrin matrices. Using both untreated and Nupr1-siRNA treated cells, we find that high Nupr1 expression prevents increase in Sox2 levels. Further, we find that Nupr1 expression is sensitive to substrate stiffness and dependent on ligand type, as Nupr1 expression increased with substrate stiffness on polyacrylamide substrates coated with col-1 but not fibrinogen. Finally, we find that Nupr1 is sensitive to stiffness in 3D culture as well, and is downstream of Cdc42-mediated cytoskeletal softening. Together, our data shows that Nupr1 responds to the physical properties of its surroundings and can regulate tumor cell plasticity via delay of Sox2 expression in 3D.
Issue Date:2015-07-22
Type:Thesis
URI:http://hdl.handle.net/2142/88298
Rights Information:Copyright 2015 Rishi Singh
Date Available in IDEALS:2015-09-29
Date Deposited:August 201


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