Although both norepinephrine and epinephrine activate CRE dependent cancer stemness, adrenergic nerves primarily produce norepinephrine in the TME.42 The kinetics of norepinephrine and epinephrine induced phospho-CREB1/ATF1 response indicate more prolonged effect on ATF1/CREB1 activation by norepinephrine (Supplementary Fig. S4j). Here, CREB1 is linked to cancer.