Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling

The lives of patients with ovarian cancer are threatened largely due to metastasis and drug resistance. Endogenous peptides attract increasing attention in oncologic therapeutic area, a few antitumor peptides have been approved by the FDA for clinical use over the past decades. However, only few peptides or peptide-derived drugs with antiovarian cancer effects have been identified. Here we focused on the biological roles and mechanism of a peptide named PDHPS1 in ovarian cancer development. Our results indicated that PDHPS1 reduced the proliferation ability of ovarian cancer cells in vitro and inhibited the ovarian cancer growth in vivo. Peptide pull down and following mass spectrometry, Western blot and qRT-PCR revealed that PDHPS1 could bind to protein phosphatase 2 phosphatase activator (PTPA), an essential activator of protein phosphatase 2A (PP2A), which resulted in increase of phosphor-ylated YAP, further inactivated YAP, and suppressed the expression of its downstream target genes. Flow cytometry, cell membrane permeability test, and IHC staining study demonstrated that there were no observable side effects of PDHPS1 on normal ovarian epithelium and hepatorenal function. Besides, modification of membrane penetration could improve the physicochemical prop-erties and biological activity of PDHPS1. In conclusion, our study demonstrated that the endogenous peptide PDHPS1 serves as an antitumor peptide to inhibit YAP signaling pathway though inter-acting with PTPA in ovarian cancer.

Automated summary

The study demonstrates that endogenous peptide PDHPS1 serves as an antitumor peptide by interacting with PTPA to inhibit the YAP signaling pathway in ovarian cancer development, showing no observable side effects on normal tissues.