RT Journal Article
T1 Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53.
A1 Ríos-Arrabal, Sandra
A1 Puentes-Pardo, Jose D
A1 Moreno-SanJuan, Sara
A1 Szuba, Ágata
A1 Casado, Jorge
A1 García-Costela, María
A1 Escudero-Feliu, Julia
A1 Verbeni, Michela
A1 Cano, Carlos
A1 González-Puga, Cristina
A1 Martín-Lagos Maldonado, Alicia
A1 Carazo, Ángel
A1 León, Josefa
K1 bosentan
K1 cancer stem cells
K1 colorectal cancer
K1 endothelin con-verting enzyme-1
K1 endothelin-1
K1 heme oxygenase-1
AB 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.
SN 2075-4426
YR 2021
FD 2021-06-04
LK https://hdl.handle.net/10668/28184
UL https://hdl.handle.net/10668/28184
LA en
DS RISalud
RD Apr 8, 2025