PTCH1
小结
PTCH1是抑癌基因，编码蛋白（蛋白质修饰的同源物1）是一种跨膜蛋白，其是致癌Hedgehog（HH）信号通路的抑制剂。PTCH1作为SHH的主要受体起作用，这是一种参与胚胎发育的分泌蛋白。PTCH1通过结合并抑制Smoothened（SMO，一种G蛋白偶联受体）来响应SHH，这导致通过HH途径的信号传导减少。因此，PTCH1通过抑制SMO介导的致癌信号传导而起到经典肿瘤抑制剂的作用。PTCH1胚系突变与痣样基底细胞癌综合征（NBCCS，Gorlin综合征）有关，携带该基因胚系突变的综合征患者具有患基底细胞癌以及成神经管细胞瘤的风险。在基底细胞癌和成神经管细胞瘤中检测到PTCH1体细胞失活突变。
PTCH1 (protein patched homolog 1) encodes a transmembrane protein that is a component of the oncogenic Hedgehog (HH) signaling pathway. PTCH1 functions as the primary receptor for sonic hedgehog (SHH), a secreted protein involved in embryonic development. In response to SHH, PTCH1 binds and inhibits Smoothened (SMO), a G protein-coupled receptor; this results in decreased signaling via the HH pathway. Thus, PTCH1 functions as a classic tumor suppressor by inhibiting SMO-mediated oncogenic signaling. Germline PTCH1 mutations are associated with the nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome), which predisposes patients to basal cell carcinoma as well as medulloblastoma. Recurrent somatic inactivating PTCH1 mutations have been identified in basal cell carcinoma and medulloblastoma, suggesting that mutant PTCH1 is a primary driver of these diseases. As inactivating PTCH1 mutations lead to increased SMO activity recently developed SMO inhibitors show promising responses in PTCH1 mutant tumors.