Ptch1, also known as Patched 1, is a tumor suppressor and serves as the receptor of Hedgehog (HH) ligand, negatively regulating the HH signaling pathway [4]. The HH signaling pathway is involved in many biological processes, and abnormal regulation of this pathway can lead to various diseases. Genetic models are valuable for studying Ptch1's function.

Mutations in Ptch1 are associated with multiple diseases. In a Chinese family, a novel heterozygous non-frameshift deletion in PTCH1 [c.3512_3526del (p.1171_1176del)] was identified, which may cause structural and functional abnormalities, leading to Gorlin-Goltz syndrome [1]. In keratocystic odontogenic tumors, PTCH1 mutations are common, with those in transmembrane 2 closely related to sporadic cases, and genetic analysis of PTCH1 should be included in new diagnostic criteria for nevoid basal cell carcinoma syndrome [2]. In non-small cell lung cancer, knockdown of Ptch1 inhibits spherical colony formation, migration, invasion, and bone destruction, suggesting it promotes anchorage-independent growth and bone invasion [3]. In colorectal and gastrointestinal cancers, Ptch1 mutations are associated with better prognosis, higher tumor mutational burden, and more antitumor immune signatures, making it a potential biomarker for immunotherapy response [5,6]. In ovarian cancer, low Ptch1 expression is related to poor prognosis, and overexpression of Ptch1 inhibits cell proliferation and promotes apoptosis [7].

In conclusion, Ptch1 plays a crucial role in negatively regulating the HH signaling pathway. Model-based research, especially through gene knockdown or mutation studies, has revealed its significance in diseases such as Gorlin-Goltz syndrome, various cancers including lung, colorectal, gastrointestinal, and ovarian cancers, as well as keratocystic odontogenic tumors. Understanding Ptch1's functions provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Yue, Hai Tang, Cao, Hai Yan, He, Miao. . Novel PTCH1 Mutation Causes Gorlin-Goltz Syndrome. In The Chinese journal of dental research, 27, 83-88. doi:10.3290/j.cjdr.b5128601. https://pubmed.ncbi.nlm.nih.gov/38546523/

2. Guo, Yan-Yan, Zhang, Jian-Yun, Li, Xue-Fen, Chen, Feng, Li, Tie-Jun. 2013. PTCH1 gene mutations in Keratocystic odontogenic tumors: a study of 43 Chinese patients and a systematic review. In PloS one, 8, e77305. doi:10.1371/journal.pone.0077305. https://pubmed.ncbi.nlm.nih.gov/24204797/

3. Choi, Ji-Yoon, Lee, Yun Sun, Shim, Da Mi, Seo, Sung Wook. 2020. PTCH1 regulates anchorage-independent growth and bone invasion of non-small cell lung cancer cells. In Bone, 144, 115829. doi:10.1016/j.bone.2020.115829. https://pubmed.ncbi.nlm.nih.gov/33359005/

4. Qi, Xiaofeng, Schmiege, Philip, Esparza, Leticia, Li, Xiaochun. . Expression, Purification, and Structure Determination of Human PTCH1-HH-N Complexes. In Methods in molecular biology (Clifton, N.J.), 2374, 107-120. doi:10.1007/978-1-0716-1701-4_10. https://pubmed.ncbi.nlm.nih.gov/34562247/

5. Wang, Yanni, Chen, Huan, Jiao, Xi, Zhang, Henghui, Shen, Lin. 2021. PTCH1 mutation promotes antitumor immunity and the response to immune checkpoint inhibitors in colorectal cancer patients. In Cancer immunology, immunotherapy : CII, 71, 111-120. doi:10.1007/s00262-021-02966-9. https://pubmed.ncbi.nlm.nih.gov/34028566/

6. Deng, Shuangya, Gu, Haoran, Chen, ZongYao, Chen, Dongsheng, Yi, Shengen. . PTCH1 mutation as a potential predictive biomarker for immune checkpoint inhibitors in gastrointestinal cancer. In Carcinogenesis, 45, 351-357. doi:10.1093/carcin/bgae007. https://pubmed.ncbi.nlm.nih.gov/38310539/

7. Zheng, Fang, Xiao, Xinyi, Wang, Chunmei. 2018. The Effect of PTCH1 on Ovarian Cancer Cell Proliferation and Apoptosis. In Cancer biotherapy & radiopharmaceuticals, 34, 103-109. doi:10.1089/cbr.2018.2626. https://pubmed.ncbi.nlm.nih.gov/30523702/