TY - JOUR
T1 - Dual oncogenic/anti-oncogenic role of PATZ1 in FRTL5 rat thyroid cells transformed by the Ha-Ras
v12
oncogene
AU - Vitiello, Michela
AU - Palma, Giuseppe
AU - Monaco, Mario
AU - Bello, Anna Maria
AU - Camorani, Simona
AU - Francesca, Paola
AU - Rea, Domenica
AU - Barbieri, Antonio
AU - Chiappetta, Gennaro
AU - de Vita, Gabriella
AU - Cerchia, Laura
AU - Arra, Claudio
AU - Fedele, Monica
PY - 2019/1/1
Y1 - 2019/1/1
N2 - PATZ1 is a transcriptional factor downregulated in thyroid cancer whose re-expression in thyroid cancer cells leads to a partial reversion of the malignant phenotype, including the capacity to proliferate, migrate, and undergo epithelial-to-mesenchymal transition. We have recently shown that PATZ1 is specifically downregulated downstream of the Ras oncogenic signaling through miR-29b, and that restoration of PATZ1 in Ha-Ras transformed FRTL5 rat thyroid cells is able to inhibit their capacities to proliferate and migrate in vitro. Here, we analyzed the impact of PATZ1 expression on the in vivo tumorigenesis of these cells. Surprisingly, FRTL5-Ras-PATZ1 cells showed enhanced tumor initiation when engrafted in nude mice, even if their tumor growth rate was reduced compared to that of FRTL5-Ras control cells. To further investigate the cause of the enhanced tumor engraftment of FRTL5-Ras-PATZ1 cells, we analyzed the stem-like potential of these cells through their capacity to grow as thyrospheres. The results showed that restoration of PATZ1 expression in these cells increases stem cell markers’ expression and self-renewal ability of the thyrospheres while limiting their growth capacity. Therefore, we suggest that PATZ1 may play a role in enhancing the stem cell potential of thyroid cancer cells, but, at the same time, it impairs the proliferation of non-stem cells.
AB - PATZ1 is a transcriptional factor downregulated in thyroid cancer whose re-expression in thyroid cancer cells leads to a partial reversion of the malignant phenotype, including the capacity to proliferate, migrate, and undergo epithelial-to-mesenchymal transition. We have recently shown that PATZ1 is specifically downregulated downstream of the Ras oncogenic signaling through miR-29b, and that restoration of PATZ1 in Ha-Ras transformed FRTL5 rat thyroid cells is able to inhibit their capacities to proliferate and migrate in vitro. Here, we analyzed the impact of PATZ1 expression on the in vivo tumorigenesis of these cells. Surprisingly, FRTL5-Ras-PATZ1 cells showed enhanced tumor initiation when engrafted in nude mice, even if their tumor growth rate was reduced compared to that of FRTL5-Ras control cells. To further investigate the cause of the enhanced tumor engraftment of FRTL5-Ras-PATZ1 cells, we analyzed the stem-like potential of these cells through their capacity to grow as thyrospheres. The results showed that restoration of PATZ1 expression in these cells increases stem cell markers’ expression and self-renewal ability of the thyrospheres while limiting their growth capacity. Therefore, we suggest that PATZ1 may play a role in enhancing the stem cell potential of thyroid cancer cells, but, at the same time, it impairs the proliferation of non-stem cells.
KW - FRTL5
KW - PATZ1
KW - Ras oncogene
KW - Stem cell biology
KW - Thyroid cancer
KW - Thyrospheres
UR - http://www.scopus.com/inward/record.url?scp=85062320793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062320793&partnerID=8YFLogxK
U2 - 10.3390/genes10020127
DO - 10.3390/genes10020127
M3 - Article
AN - SCOPUS:85062320793
VL - 10
JO - Genes
JF - Genes
SN - 2073-4425
IS - 2
M1 - 127
ER -