Controlling secretion to limit chemoresistance.
The tumor microenvironment influences cancer progression and therapy outcome by mechanisms not yet fully understood. In this issue of Genes & Development, Bent and colleagues (pp. 1811-1821) show how chemotherapy causes endothelial senescence. Interestingly, senescent endothelial cells do not mount a typical senescence-associated secretory phenotype but instead acutely secrete IL-6, promoting chemoresistance. This study unveils a physiological switch involving PI3K/AKT/mTOR signaling that restrains the senescence secretory responses to limit the detrimental consequences of persistent inflammation.
MRC Clinical Sciences Centre (CSC), London W12 0NN, United Kingdom; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
Athena
A
Georgilis
MRC Clinical Sciences Centre (CSC), London W12 0NN, United Kingdom; Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom.
Jesús
J
Gil
D016922:Cellular Senescence / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*
D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases
SASP; chemoresistance; endothelial cell; paracrine; senescence; tumor microenvironment