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Peptide PDHPS1 Inhibits Ovarian Cancer Growth through Disrupting YAP Signaling
Xinxing Pan1, Zhe Geng1, Jingyun Li2
1Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.
Abstract:
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 phosphorylated 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 properties 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 interacting with PTPA in ovarian cancer.
Insights
The endogenous peptide PDHPS1 inhibits ovarian cancer growth by targeting the YAP signaling pathway. This novel antitumor peptide shows no observable side effects on normal tissues.
Area of Science:
- Oncology
- Molecular Biology
- Peptide Therapeutics
Background:
- Ovarian cancer metastasis and drug resistance pose significant threats to patients.
- Endogenous peptides are emerging as promising therapeutic agents in oncology.
- Few anti-ovarian cancer peptides have been identified, highlighting a need for new therapeutic strategies.
Purpose of the Study:
- To investigate the biological roles and mechanism of the endogenous peptide PDHPS1 in ovarian cancer development.
- To evaluate the therapeutic potential of PDHPS1 against ovarian cancer.
Main Methods:
- In vitro and in vivo studies to assess PDHPS1's effect on ovarian cancer cell proliferation and tumor growth.
- Peptide pull-down assays, mass spectrometry, Western blot, and qRT-PCR to identify PDHPS1's molecular targets.
- Flow cytometry, cell membrane permeability tests, and IHC staining to evaluate PDHPS1's safety profile.
Main Results:
- PDHPS1 significantly reduced ovarian cancer cell proliferation in vitro and inhibited tumor growth in vivo.
- PDHPS1 binds to protein phosphatase 2 phosphatase activator (PTPA), increasing phosphorylated YAP and suppressing its downstream target genes.
- PDHPS1 demonstrated no observable side effects on normal ovarian epithelium and hepatorenal function.
Conclusions:
- The endogenous peptide PDHPS1 acts as an antitumor agent by inhibiting the YAP signaling pathway through interaction with PTPA in ovarian cancer.
- PDHPS1 represents a potential therapeutic candidate for ovarian cancer treatment.
- Modifications to enhance membrane penetration could further improve PDHPS1's therapeutic efficacy.
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