Fig. 7
From: Androgen receptor variant-7 regulation by tenascin-c induced src activation
Model of regulation of AR-V7 in prostate cancer cells interacting with Preosteoblast and TNC. A Prostate cancer cells interact with preosteoblast forming 3D heterotypical organoids. The preosteoblast organizes to form the inner core and prostate cancer cells compartmentalize around the preosteoblast. TNC is secreted by preosteoblast onto its surface in regions of contact with prostate cancer cells. Both TNC and AR-V7 transcript levels are upregulated in prostate cancer cells interacting with preosteoblast, which is further induced by Enzalutamide (Enz) and suppressed by Testosterone (Test). The 3D heterotypical organoid depicted is composed of VCaP and mouse preosteoblasts-MC3T3-E1. The live cell image of the 3D heterotypical organoids was captured using 20 × objective. B TNC induce Src activation in prostate cancer cells regulating AR-V7 splicing and stability. This suggests a positive feedback effect where the osteogenic microenvironment components like preosteoblasts and TNC can select for AR-V7 in prostate cancer cells via Src activation. Reciprocally both AR-V7 and activated Src regulate autocrine TNC expression in prostate cancer cells further modifying the osteogenic microenvironment. The image was created with Biorender.com