@misc{10481/111391,
year = {2025},
month = {1},
url = {https://hdl.handle.net/10481/111391},
abstract = {PARP-1 has been linked to the progression of several types of cancer. We have recently reported that PARP-1 influences tumor progression in CRC through the regulation of CSCs in a p53-dependent manner. In this study, we propose that nitric oxide (NO)
produced by inducible nitric oxide synthase (iNOS) could act as a mediator. We evaluated the expression of iNOS in a cohort of patients previously used to analyze the effects of PARP-1 on CRC in relation to p53 status. We also developed an in vitro model in which PARP-1 was stably overexpressed. In CRC patients, iNOS expression correlated with the differentiation grade, and with a high expression of CSC markers, although only in wild-type p53 tumors, as previously found for PARP-1. In vitro, overexpression of PARP-1
induced increased growth and stemness in wild-type p53 cells, while exerting the opposite effect on mutated ones, as expected. Treatment with 1400 W, a selective inhibitor of iNOS, or gene silencing of the gene counteracted the effects of PARP-1 in both p53 wild-type and p53 mutated cells. Given that the development of resistance has been demonstrated after treatment with PARP-1 inhibitors, iNOS could be considered a new therapeutic target in CRC, although only in patients with wild-type p53 tumors.},
organization = {Instituto de Salud Carlos III-FEDER (PI21/01378 and FI23/00234)},
organization = {Consejería de Salud},
organization = {Junta de Andalucía (PI-067/2013)},
organization = {Andalusian Health Service (C-0033-2015)},
publisher = {MDPI},
keywords = {Colorectal cancer (CRC)},
keywords = {PARP1},
keywords = {iNOS},
title = {iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer},
doi = {10.3390/biom15010125},
author = {Moral Martínez, María del and Sánchez-Uceta, Paula and Clemente González, Rubén and San Juan, Sara Moreno and Puentes Pardo, José David and Khaldy, Huda and López Pérez, David and Arnedo Fernández, Francisco Javier and Casado, Jorge and Martínez Heredia, Luis and Carazo, Ángel and León, Josefa},
}