Mechanical and epigenetic regulation of cell plasticity and tumorigenicity

Nuclear Protein 1 (Nupr1);Sox2;tumorigenesis;plasticity;cancer;epigenetics;mechanics;tumor microenvironment

Singh, Rishi Bal ; Wang ; Ning

关键词: Nuclear Protein 1 (Nupr1);    Sox2;    tumorigenesis;    plasticity;    cancer;    epigenetics;    mechanics;    tumor microenvironment;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/88298/SINGH-THESIS-2015.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

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.