CXCL12/CXCR4 Axis Activation Mediates Prostate Myofibroblast Phenoconversion through Non-Canonical EGFR/MEK/ERK Signaling
Fig 1
CXCL12/CXCR4 axis-mediated myofibroblast phenoconversion is not coupled to Smad3 phosphorylation.
N1 fibroblasts (A) and primary prostate fibroblasts (B) were treated in defined serum-free Ham’s media with CXCL12 (100pM), or 0.01% BSA vehicle, and TGFβ (4 ng/mL) or 20mM citric acid vehicle. In both types of cells EGFR, Akt and Erk1/2 were phosphorylated upon CXCL12 treatment. TGFβ treatment activated Smad-mediated signaling and transient Erk1/2 phosphorylation, but not EGFR or Akt phosphorylation. Total antibodies for each kinase, as well as GAPDH and actin, were used as loading control. Protein molecular weight in kilodaltons is indicted by arrows. Signal intensity quantification (C) for N1 fibroblasts shows that EGFR activation occurs at 5 minutes post-treatment, followed by a robust activation of Erk at 10 minutes as well as mild Akt activation. The same pattern was observed in primary fibroblasts (D), however EGFR activation surpassed that of Erk.