CXCL12/CXCR4 Axis Activation Mediates Prostate Myofibroblast Phenoconversion through Non-Canonical EGFR/MEK/ERK Signaling
Fig 6
Proposed mechanism of action used by CXCL12 to drive myofibroblast phenoconversion.
The canonical pathway driving myofibroblast differentiation is driven by TGF-β-mediated Smad and MEK/Erk signaling14. However, upon binding to CXCR4, CXCL12 promotes the transactivation of EGFR, potentially through MMP/ADAM as previously described by Kasina et.al in prostate cancer cells35 and Src activation, as shown in the supplementary data (S2 Fig). Active EGFR then activates Akt and MEK/ERK signaling pathways to promote myofibroblast marker gene expression and phenoconversion. CXCL12-mediated phenoconversion acts independently of TGFβR/Smad-mediated myofibroblast phenoconversion.