PACT Inhibits Malignant Biological Behavior of Ovarian Cancer Cells by Regulating TERT Expression
Year: 2026
Type: article
Abstract: Ovarian cancer (OC) is a lethal malignancy with limited treatment options. While p53-associated cellular protein-testes derived (PACT) has been implicated in cellular stress responses, its role in OC progression and the regulation of ferroptosis remains unclear. The functional role of PACT was examined in A2780 and OVCAR-3 cells through siRNA-mediated knockdown and overexpression. The CCK-8 assay was used to evaluate cell proliferation, and the transwell assay was used to detect cell migration and invasion. Ferroptosis was assessed by measuring cell death, iron content, malondialdehyde (MDA), reactive oxygen species (ROS), and the expression of key proteins (SLC7A11, GPX4). Molecular mechanisms were investigated via co-immunoprecipitation (Co-IP), ubiquitination assays, and analysis of subcellular localization. In vivo validation was conducted using a xenograft model in BALB/c nude mice. The results showed that PACT knockdown significantly inhibited the proliferation, migration, and invasion of OC cells. It also promoted ferroptosis, as indicated by elevated iron accumulation, lipid peroxidation, and ROS levels, along with reduced SLC7A11 and GPX4 expression-effects that were reversed by ferrostatin-1. PACT was found to enhance TERT expression and telomerase activity via the Keap1-Nrf2 pathway by facilitating Keap1 ubiquitination and degradation, which promoted Nrf2 nuclear translocation. Importantly, Nrf2 knockdown abolished PACT-mediated TERT upregulation. In vivo, PACT silencing suppressed tumor growth and induced ferroptosis. In conclusion, PACT promotes OC progression by suppressing ferroptosis and enhancing malignant phenotypes through the Keap1-Nrf2-TERT axis. These findings suggest that targeting PACT may represent a promising therapeutic strategy for OC.
Source: Molecular Carcinogenesis
DOI: 10.1002/mc.70141
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7168909168