The P2X7 receptor for extracellular ATP has long being known as ion channel involved in Interleukin 1 release and immune system regulation. More recently , we demonstrated a role for P2X7 in cellular homeostasis consisting in an increase of mitochondrial and reticular calcium levels that leads to intracellular ATP production and cell growth (1- 3). Expression of P2X7 receptor in several cancer models is widely reported but studies directly linking in vivo tumorigenesis with receptor function were missing. Here we demonstrated that P2X7 receptor increases tumor growth in vivo both in xenograft and syngeneic mice models (4). This effect is partially mediated by increased tumoral cell growth and activation of the HIF-1 alpha, VEGF axis. Moreover, administration of P2X7 blocking drugs effectively reduces tumor growth in mice models of melanoma and neuroblastoma suggesting that the P2X7 receptor as a good pharmacological target for cancer therapeutics. References 1. E. Adinolfi et al., Mol. Biol. Cell 16, 3260 (2005). 2. E. Adinolfi et al., FASEB J. 24, 3393 (2010). 3. E. Adinolfi et al., J. Biol. Chem. 284, 10120 (2009). 4. E. Adinolfi et al., Cancer Res. 72, 2957 (2012).
The P2X7 receptor : from ion channel to oncogene
ADINOLFI, Elena;CAPECE, Marina;AMOROSO, Francesca Saveria;FRANCESCHINI, Alessia;GIULIANI, Anna Lisa;DI VIRGILIO, Francesco
2013
Abstract
The P2X7 receptor for extracellular ATP has long being known as ion channel involved in Interleukin 1 release and immune system regulation. More recently , we demonstrated a role for P2X7 in cellular homeostasis consisting in an increase of mitochondrial and reticular calcium levels that leads to intracellular ATP production and cell growth (1- 3). Expression of P2X7 receptor in several cancer models is widely reported but studies directly linking in vivo tumorigenesis with receptor function were missing. Here we demonstrated that P2X7 receptor increases tumor growth in vivo both in xenograft and syngeneic mice models (4). This effect is partially mediated by increased tumoral cell growth and activation of the HIF-1 alpha, VEGF axis. Moreover, administration of P2X7 blocking drugs effectively reduces tumor growth in mice models of melanoma and neuroblastoma suggesting that the P2X7 receptor as a good pharmacological target for cancer therapeutics. References 1. E. Adinolfi et al., Mol. Biol. Cell 16, 3260 (2005). 2. E. Adinolfi et al., FASEB J. 24, 3393 (2010). 3. E. Adinolfi et al., J. Biol. Chem. 284, 10120 (2009). 4. E. Adinolfi et al., Cancer Res. 72, 2957 (2012).I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
