PDE4 inhibitor rolipram represses hedgehog signaling via ubiquitin-mediated proteolysis of GLI transcription factors to regress breast cancer.

ABSTRACT: Aberrant activation of the Hedgehog (Hh) signaling pathway positively correlates with progression, invasion, and metastasis of several cancers, including breast cancer. Although numerous inhibitors of the Hh signaling pathway are available, several oncogenic mutations of key components of the pathway, including Smoothened, have limited their capability to be developed as putative anticancer drugs. In this study, we have modulated the Hh signaling pathway in breast cancer using a specific Food and Drug Administration-approved phosphodiesterase 4 inhibitor rolipram. The results indicated that increased levels of cAMP-dependent PKA, because of the treatment with rolipram on MCF-7 and MDA-MB-231 cells, induced PKA-mediated ubiquitination of glioma-associated oncogene homolog 2 full length (GLI

SUBMITTER: Bagchi A 

PROVIDER: S-EPMC11879692 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature