RGS5+ lymphatic endothelial cells facilitate metastasis and acquired drug resistance of breast cancer through oxidative stress-sensing mechanism.
Drug Resist Updat
; 77: 101149, 2024 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-39306871
ABSTRACT
AIMS:
Oxidative stress reflected by elevated reactive oxygen species (ROS) in the tumor ecosystem, is a hallmark of human cancers. The mechanisms by which oxidative stress regulate the metastatic ecosystem and resistance remain elusive. This study aimed to dissect the oxidative stress-sensing machinery during the evolvement of early dissemination and acquired drug resistance in breast cancer.METHODS:
Here, we constructed single-cell landscape of primary breast tumors and metastatic lymph nodes, and focused on RGS5+ endothelial cell subpopulation in breast cancer metastasis and resistance.RESULTS:
We reported on RGS5 as a master in endothelial cells sensing oxidative stress. RGS5+ endothelial cells facilitated tumor-endothelial adhesion and transendothelial migration of breast cancer cells. Antioxidant suppressed oxidative stress-induced RGS5 expression in endothelial cells, and prevented adhesion and transendothelial migration of cancer cells. RGS5-overexpressed HLECs displayed attenuated glycolysis and oxidative phosphorylation. Drug-resistant HLECs with RGS5 overexpression conferred acquired drug resistance of breast cancer cells. Importantly, genetic knockdown of RGS5 prevented tumor growth and lymph node metastasis.CONCLUSIONS:
Our work demonstrates that RGS5 in lymphatic endothelial cells senses oxidative stress to promote breast cancer lymph node metastasis and resistance, providing a novel insight into a potentially targetable oxidative stress-sensing machinery in breast cancer treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Drug Resist Updat
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2024
Tipo de documento:
Article