2026-09-21T04:24:55Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/88298 2023-07-11 col_2142_5131 col_2142_14787 com_2142_5130 com_2142_9630 com_2142_234

Made available in DSpace on 2015-09-29T21:08:15Z (GMT). No. of bitstreams: 2 SINGH-THESIS-2015.pdf: 283696 bytes, checksum: 0f7e963da95634dafa16e9e9a970da45 (MD5) LICENSE.txt: 4208 bytes, checksum: dd735d55c1189c6cc1ef21be4dc1ab2c (MD5) Previous issue date: 2015-07-22 Embargo set by: Seth Robbins for item 89579 Lift date: 2017-09-29T21:08:35Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD system Limited Restriction Lifted for Item 89579 on 2017-09-30T09:15:27Z. application/pdf http://hdl.handle.net/2142/88298 en Copyright 2015 Rishi Singh Nuclear Protein 1 (Nupr1) Sox2 tumorigenesis plasticity cancer epigenetics mechanics tumor microenvironment Mechanical and epigenetic regulation of cell plasticity and tumorigenicity text text Wang, Ning Singh, Rishi Bal 2015-09-29T21:08:15Z 2015-09-29T21:08:15Z 2017-09-30T09:15:27Z 2015-08 2015-07-22 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. Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-08-01 The student, Rishi Singh, accepted the attached license on 2015-07-21 at 15:33. The student, Rishi Singh, submitted this Thesis for approval on 2015-07-21 at 15:37. This Thesis was approved for publication on 2015-07-22 at 08:44. DSpace SAF Submission Ingestion Package generated from Vireo submission #8542 on 2015-09-29 at 15:06:34 2015-8 Mechanical Science & Engineering Mechanical Engineering University of Illinois at Urbana-Champaign Thesis M.S.