CLOCK and cancer: To further identify the mechanism of chronic stress-induced NE modulates circadian clock to promote cancer stemness, we established ADRB2 stable knockdown cells by shRNAs [26] in NCI-H1299 cells and found that ADRB2 deficiency reversed NE-induced CLOCK and stemness-related factors NANOG, OCT4, SOX2 and CD166 level (Fig. 4A-C).