PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation.

ABSTRACT: Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1^fl/fl ; Gli1-Cre^ERT2 mouse BCCs with the PI3K inhibitor B

SUBMITTER: Chow RY 

PROVIDER: S-EPMC8276170 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature