Patched1 Functions as a Gatekeeper by Promoting Cell Cycle Progression

The study demonstrated that the loss of Patched 1 (Ptch1) function in the basal cell population of mouse skin was sufficient to induce rapid skin tumor formation, similar to human basal cell carcinoma (BCC). The research showed that Ptch1 did not affect the nuclear translocation of β-catenin or activate the Notch pathway, but its absence led to the nuclear accumulation of cell cycle regulators cyclin D1 and B1. This suggested that Ptch1 acted as a tumor suppressor by inhibiting cell cycle progression at the G1-S and G2-M phases, functioning as a "gatekeeper." The mouse model used in this study, due to its high frequency and rapid onset of tumors, was considered ideal for testing therapeutic strategies, including Patched pathway inhibitors.