Molecular Targeting of Cancer-Associated PCNA Interactions in Pancreatic Ductal Adenocarcinoma Using a Cell-Penetrating Peptide.
Cell death
Cell-penetrating peptide
DNA damage
DNA damage response
DNA repair
PCNA
Pancreatic Cancer
Peptide therapeutics
Proliferating cell nuclear antigen
Replication Stress
Journal
Molecular therapy oncolytics
ISSN: 2372-7705
Titre abrégé: Mol Ther Oncolytics
Pays: United States
ID NLM: 101666776
Informations de publication
Date de publication:
26 Jun 2020
26 Jun 2020
Historique:
received:
10
02
2020
accepted:
31
03
2020
entrez:
6
5
2020
pubmed:
6
5
2020
medline:
6
5
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32368614
doi: 10.1016/j.omto.2020.03.025
pii: S2372-7705(20)30050-4
pmc: PMC7190754
doi:
Types de publication
Journal Article
Langues
eng
Pagination
250-256Subventions
Organisme : NCI NIH HHS
ID : R01 CA225843
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127602
Pays : United States
Informations de copyright
© 2020 The Author(s).
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