Mechanical and epigenetic regulation of cell plasticity and tumorigenicity
Singh, Rishi Bal
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https://hdl.handle.net/2142/88298
Description
Title
Mechanical and epigenetic regulation of cell plasticity and tumorigenicity
Author(s)
Singh, Rishi Bal
Issue Date
2015-07-22
Director of Research (if dissertation) or Advisor (if thesis)
Wang, Ning
Department of Study
Mechanical Science & Engineering
Discipline
Mechanical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(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.
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