Panoply™ Human SMO Knockdown Stable Cell Line

Hedgehog (Hh) signaling promotes castration-resistant prostate cancer by supporting the development and growth of androgen-independent prostate cancer cells. However, its role in neuroendocrine prostate cancer (NEPC) has been less well-studied. Here, researchers evaluated the expression of key genes involved in Hh signaling in prostate cancer and explored the potential role of smooth muscle cell (SMO) in the pathogenesis of NEPC. They analyzed six public datasets, each containing prostate adenocarcinoma (AdPC) and NEPC cases, to compare the differential messenger RNA (mRNA) expression of six canonical Hh signaling genes. Results showed that SMO mRNA levels were significantly downregulated in NEPC samples across all six public datasets, while SMO mRNA levels were significantly downregulated in AdPC samples. SMO protein loss was observed in 100% of NEPC samples, but only in 9% of high-grade AdPC samples. GSEA results showed that SMO loss was closely associated with AR signaling activity. Stable SMO knockdown significantly attenuated AR signaling and suppressed AR expression, whereas Gli1 overexpression partially reversed the inhibitory effects of SMO knockdown on AR signaling and expression in LNCaP and C4-2B cells. These results suggest that SMO deficiency is a hallmark of NEPC and that immunohistochemical (IHC) detection of SMO may aid pathologists in diagnosing NEPC. SMO deficiency may contribute to the pathogenesis of NEPC by modulating AR signaling.

Here, researchers established stable SMO knockdown LNCaP and C4-2B cell lines to evaluate the effect of SMO loss on AR signaling. As shown in Figures 1A and B, AR and PSA expression was reduced in SMO knockdown cells compared with control cells, while the expression levels of NE markers were not significantly different.

Figure 1. Knockdown of SMO inhibits AR pathway activity and reduces AR expression. (Wang L, et al., 2021)