Fig. 4: cGMP-PKG signaling mediates psychological stress-induced stem-like phenotypes and tumor development.

A A schematic of the timing of chronic restraint stress, tumor inoculation, PKGi injections, behavioral tests and sample collection in the PY8119 syngeneic tumor model. B, C Representative tumor image (B) and growth curve (C) of Ctrl, Stress, PKGi and Stress plus PKGi PY8119 tumor in mice (n = 6). D Relative protein levels of sGC and phosphorylation level of VASP (Ser239) were determined following in PY8119 tumor (in A). E Relative mRNA levels of Sox2, Nanog and Ctnnb1 were determined following in PY8119 tumor (n = 6). F Representative images of SOX2, NANOG and β-Catenin IHC staining in PY8119 tumor. Scale bars, 50 μm. G Relative protein levels of sGC and phosphorylation level of VASP (Ser239) were determined following Epi and PKGi treatment in MDA-MB-231 cells. H ALDH-positive populations were analyzed following treatment Epi and PKGi in MDA-MB-231 cells (n = 3). I Sphere formation ability was analyzed following treatment Epi and PKGi in MDA-MB-231 cells. The representative images were presented (Left, scale bar = 100 μm) and the number (Middle) and diameter (Right) of spheroids were measured and counted (n = 4). Epi, epinephrine. Graph data were presented as mean ± SD. **P < 0.01, ****P < 0.0001. P-values were calculated with two-tailed, unpaired Student’s t-test (C) or one-way ANOVA (E, H, I).