Reduced PTCH2 expression is associated with glioma development through its regulation of the PTEN/AKT signaling pathway

Mutations in the human protein patched homolog (PTCH) gene have been demonstrated to be associated with cancer development in several types of malignancy. However, the underlying mechanism of PTCH-associated cancer development remains poorly understood, to the best of our knowledge. In the present study, the expression of PTCH2 in glioma tumor tissues from The Cancer Genome Atlas (TCGA) database and clinical patients with glioma were measured. Reduced expression levels of PTCH2 were observed in patients with glioma with poor prognose. In vitro, overexpression of PTCH2 significantly suppressed the proliferation and invasion of the glioma cell lines, LN229 and U87-MG. Mechanistically, PTCH2 upregulated the expression of tumor suppressor PTEN, thereby leading to the suppression of pro-survival AKT signals in glioma. Reduced expression of PTEN and enhanced expression of AKT promoted glioma development in vitro and in vivo. Blockade of PTCH2/AKT signals efficiently strengthened the anticancer effects of chemotherapy and prolonged the survival time in tumor-bearing mice, which provided a novel insight into potential treatment strategies for glioma in the clinic.