The loss of <i>Tp53</i> and <i>Tsc1</i> within nestin-expressing cells in mice resulted in the development of renal cell carcinomas (RCC) with high <i>Notch1</i> and <i>Nodal</i> expression, suggesting that similar downstream mechanisms contribute to tumorigenesis as a result of p53 loss in mice and p53 polymorphism in humans.
These findings highlight the novel function of Nestin in regulating Shh signaling, as well as the important role of a disrupted negative feedback mechanism in MB tumorigenesis.
GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice.
The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors.
Collectively, our findings indicate that Nestin, which is downregulated by miR-940, can promote tumorigenesis in NPC cells through involvement in the DNA damage response.
Importantly, C6 subclones that expressed nestin at low levels in vitro were also found to give rise to tumors highly positive for the protein, suggesting that induction of nestin plays an important role in glioblastoma carcinogenesis.