Expression of the P2X7 receptor and metabolic adaptation in serum and glucose deprivation

One of the main features in cancers is the adaptation to stressing conditions. This adaptation confers them the ability to grow under reduced nutrient availability shape. Several findings point to the PI3K/Akt pathway as the main pathway involved. Lately, adaptation to glucose deprivation, as well as to serum starvation, is considered a crucial event in tumour progression. Recently, in our laboratory, we have demonstrated a close relationship between expression of the P2X7 receptor and increased proliferation in the absence of serum (Adinolfi et al. 2009). Here, we analyze the adaptation of HEK293 cells stably expressing the P2X7 receptor (HEK293-P2X7) to two key metabolic stress factors: glucose deprivation and serum starvation. In the absence of glucose (4 mM), HEK293-P2X7 have a higher growth rate compared with HEK293 cells transfected with the empty vector (HEK293-mock). In addition, HEK293-P2X7 are shown to produce twofold more ATP and release twice as much lactate (p<0.05) than HEK293-mock. Moreover, in the absence of serum, PKM2 and PDHK1 are overexpressed in HEK293-P2X7 and are hypermodulated by the glucose deprivation. GLUT1 is overexpressed in HEK293-P2X7. Akt is activated in HEK293-P2X7. These observations suggest a higher efficiency in glucose uptake and employment by HEK293-P2X7, explaining a possible role for the P2X7 receptor in cancer cell survival.