@misc{10481/69009,
year = {2021},
url = {http://hdl.handle.net/10481/69009},
abstract = {Heme oxygenase-1 (HO-1) is an antioxidant protein implicated in tumor progression,
metastasis, and resistance to therapy. Elevated HO-1 expression is associated with stemness in several
types of cancer, although this aspect has not yet been studied in colorectal cancer (CRC). Using an
in vitro model, we demonstrated that HO-1 overexpression regulates stemness and resistance to
5-FU treatment, regardless of p53. In samples from CRC patients, HO-1 and endothelin converting
enzyme-1 (ECE-1) expression correlated significantly, and p53 had no influence on this result. Carbon
monoxide (CO) activated the ECE-1/endothelin-1 (ET-1) pathway, which could account for the
protumoral effects of HO-1 in p53 wild-type cells, as demonstrated after treatment with bosentan (an
antagonist of both ETRA and ETRB endothelin-1 receptors). Surprisingly, in cells with a non-active
p53 or a mutated p53 with gain-of-function, ECE-1-produced ET-1 acted as a protective molecule,
since treatment with bosentan led to increased efficiency for spheres formation and percentage of
cancer stem cells (CSCs) markers. In these cells, HO-1 could activate or inactivate certain unknown
routes that could induce these contrary responses after treatment with bosentan in our cell model.
However more research is warranted to confirm these results. Patients carrying tumors with a
high expression of both HO-1 and ECE-1 and a non-wild-type p53 should be considered for HO-1
based-therapies instead of ET-1 antagonists-based ones.},
organization = {Instituto de Salud Carlos IIIFEDER (PI18/01947)},
organization = {MINECO grant (DPI2017-84439-R)},
organization = {Nicolás
Monardes Program from the Andalusian Health Service (C-0033-2015)},
organization = {FPU2019 fellowship (FPU19/02269) from the Ministerio de Ciencia, Innovación y Universidades
(Spain)},
publisher = {MDPI},
keywords = {Colorectal cancer},
keywords = {Cancer stem cells},
keywords = {Heme oxygenase-1},
keywords = {Endothelin-1},
keywords = {Endothelin converting enzyme-1},
keywords = {Bosentan},
title = {Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53},
doi = {10.3390/jpm11060509},
author = {Ríos Arrabal, Sandra and Puentes Pardo, José David and Moreno San Juan, Sara and Casado, Jorge and García Costela, María and Escudero Feliú, Julia and Verbeni, Michela and Cano Gutiérrez, Carlos and González Puga, María Cristina and Martín-Lagos Maldonado, Alicia and Carazo Gallego, Ángel and León López, Josefa},
}