Background An increased ATP concentration is a typical biochemical feature of the tumor microenvironment (TME). Likewise, many malignant tumors overexpress plasma membrane receptors for extracellular ATP (P2Rs), and P2Rs play a role in cancer cell intravasation/extravasation and therefore in metastatic spreading. These observations highlight the importance of purinergic signalling in cancer research. A substantial breakthrough in the biochemistry and cell biology of extracellular ATP has been the generation of a bioluminescent probe allowing the in vivo real-time measurement of the extracellular ATP concentration. This probe, named plasma membrane luciferase (pmeLUC) has allowed to unequivocally demonstrate that the TME is a "high-ATP environment", and that ATP within this environment can be used by cancer cells to support their metabolic requirements. Among the P2Rs, P2X7R is mostly involved in cancer as: a) is upregulated in cancer cells; b) promotes growth; c) stimulates the Warburg effect; d) is necessary for metastatic spreading. In addition, P2X7R is intimately linked to the NLRP3 inflammasome.
The P2X7 receptor: a key determinant of cellular metabolic energetics in cancer progression - AIRC IG 18581
DI VIRGILIO, Francesco
2016
Abstract
Background An increased ATP concentration is a typical biochemical feature of the tumor microenvironment (TME). Likewise, many malignant tumors overexpress plasma membrane receptors for extracellular ATP (P2Rs), and P2Rs play a role in cancer cell intravasation/extravasation and therefore in metastatic spreading. These observations highlight the importance of purinergic signalling in cancer research. A substantial breakthrough in the biochemistry and cell biology of extracellular ATP has been the generation of a bioluminescent probe allowing the in vivo real-time measurement of the extracellular ATP concentration. This probe, named plasma membrane luciferase (pmeLUC) has allowed to unequivocally demonstrate that the TME is a "high-ATP environment", and that ATP within this environment can be used by cancer cells to support their metabolic requirements. Among the P2Rs, P2X7R is mostly involved in cancer as: a) is upregulated in cancer cells; b) promotes growth; c) stimulates the Warburg effect; d) is necessary for metastatic spreading. In addition, P2X7R is intimately linked to the NLRP3 inflammasome.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
