Modulation of androgen and Perlecan regulated Sonic Hedgehog signaling. As changes occur to the tumor microenvironment, prostate cancer cells modulate their use of both androgen and Perlecan mediated Sonic Hedgehog signaling. The use of androgen (T) occurs via the androgen receptor (AR). Perlecan (P) is produced, binds Sonic Hedgehog (S) and signals through the Gli (G) proteins. The heaviness of each arrow indicates relative signaling strength (gene expression, complex formation). Androgen sensitive cells (LNCaP) utilize both androgen and Perlecan-SHH signaling under normal conditions, but decrease Perlecan-SHH signaling under poor growth conditions. In contrast aggressive androgen insensitive cells (C4, C4-2, C4-2B) utilize both pathways, and upregulate the Perlecan-SHH signaling under poor growth conditions. This may occur through increased SHH binding affinity to Perlecan.