Fig. 8: Schematic representation of the Fos/AP-1-Wnt7b/Wnt9a-Loxl2 axis operating in OS formation.
From: Wnt signaling and Loxl2 promote aggressive osteosarcoma
Wnt9a and Wnt7b are two novel c-Fos/AP-1 target genes operating in an autocrine, and possibly paracrine, fashion in mouse and human OS to induce the expression of the collagen cross-linking enzyme Loxl2, thereby modulating collagen packing and impacting on osteoblast differentiation and tumor aggressiveness. c-Fos protein expression and stability is maintained through EGFR and its downstream kinase RSK2 and the new regulatory pathway can be therapeutically targeted by inhibiting Wnt secretion (Wls) and/or Loxl2 activity (BAPN or blocking antibodies), to benefit OS patients.
