CXCL12/CXCR4 Axis Activation Mediates Prostate Myofibroblast Phenoconversion through Non-Canonical EGFR/MEK/ERK Signaling
Fig 2
CXCL12/CXCR4-mediated signaling and myofibroblast phenoconversion requires EGFR transactivation.
(A) N1 fibroblasts were pre-treated with chemical inhibitors of CXCR4 (25 μM AMD3100), EGFR (500 nM AG1478), and TGFβRI (500 nM SB431542) or with 50 ng/ml EGF or 4ng/ml TGFβ for three hours. No activation of downstream signaling kinases (Akt, smad3, Erk) was observed in inhibitor-only treatment of fibroblasts. (B) N1 fibroblasts were pre-treated with chemical inhibitors of CXCR4 (25 μM AMD3100), EGFR (500 nM AG1478), and TGFβRI (500 nM SB431542) for two hours prior to CXCL12 (100 pM) treatment. Treatment with AMD3100 and AG1478 completely ablated the phosphorylation and activation of downstream targets. Inhibition of TGFβRI activation, with SB431542, had no effect of CXCL12 signaling.