Bibliographic Details
| Title: |
Molecular Targeting of Cancer-Associated PCNA Interactions in Pancreatic Ductal Adenocarcinoma Using a Cell-Penetrating Peptide |
| Authors: |
Shanna J. Smith, Caroline M. Li, Robert G. Lingeman, Robert J. Hickey, Yilun Liu, Linda H. Malkas, Mustafa Raoof |
| Source: |
Molecular Therapy: Oncolytics, Vol 17, Iss , Pp 250-256 (2020) |
| Publisher Information: |
Elsevier, 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Pancreatic Cancer, PCNA, DNA repair, Cell-penetrating peptide, DNA damage, Replication Stress, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Pancreatic ductal adenocarcinoma is a particularly difficult cancer to treat due to a lack of effective screening or treatment. Pancreatic cancer cells exhibit high proliferating cell nuclear antigen (PCNA) expression, which is associated with poor prognosis. PCNA, an important nuclear DNA replication and repair protein, regulates a myriad of proteins via the interdomain connector loop. Within this region, amino acids 126–133 are critical for PCNA interactions in cancer cells. Here, we investigate the ability of a decoy cell-penetrating peptide, R9-caPeptide, that mimics the interdomain connector loop region of PCNA to disrupt PCNA-protein interactions in pancreatic cancer cells. Our data suggest that R9-caPeptide causes dose-dependent toxicity in a panel of pancreatic cancer cell lines by inhibiting DNA replication fork progression and PCNA-regulated DNA repair, ultimately causing lethal DNA damage. Overall, these studies lay the foundation for novel therapeutic strategies that target PCNA in pancreatic cancer. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2372-7705 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2372770520300504; https://doaj.org/toc/2372-7705 |
| DOI: |
10.1016/j.omto.2020.03.025 |
| Access URL: |
https://doaj.org/article/a1ad7611a80949079f0a82b199712e39 |
| Accession Number: |
edsdoj.1ad7611a80949079f0a82b199712e39 |
| Database: |
Directory of Open Access Journals |
