Malignant cell-specific pro-tumorigenic role of type I interferon receptor in breast cancers

Within the microenvironment of solid tumors, stress associated with deficit of nutrients and oxygen as well as tumor-derived factors triggers the phosphorylation-dependent degradation of the IFNAR1 chain of type I interferon (IFN1) receptor and ensuing suppression of the IFN1 pathway. Here we sought...

Full description

Saved in:
Bibliographic Details
Published in:Cancer biology & therapy 2020-07, Vol.21 (7), p.629-636
Main Authors: Odnokoz, Olena, Yu, Pengfei, Peck, Amy R., Sun, Yunguang, Kovatich, Albert J., Hooke, Jeffrey A., Hu, Hai, Mitchell, Edith P., Rui, Hallgeir, Fuchs, Serge Y.
Format: Article
Language:English
Subjects:
breast cancer
IFNAR1
immune therapy
interferon receptor
mammary adenocarcinoma
PD-L1
Research Paper
type I interferon
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Within the microenvironment of solid tumors, stress associated with deficit of nutrients and oxygen as well as tumor-derived factors triggers the phosphorylation-dependent degradation of the IFNAR1 chain of type I interferon (IFN1) receptor and ensuing suppression of the IFN1 pathway. Here we sought to examine the importance of these events in malignant mammary cells. Expression of non-degradable IFNAR1 S526A mutant in mouse mammary adenocarcinoma cells stimulated the IFN1 pathway yet did not affect growth of these cells in vitro or ability to form subcutaneous tumors in the syngeneic mice. Remarkably, these cells exhibited a notably accelerated growth when transplanted orthotopically into mammary glands. Importantly, in human patients with either ER+ or ER- breast cancers, high levels of IFNAR1 were associated with poor prognosis. We discuss the putative mechanisms underlying the pro-tumorigenic role of IFNAR1 in malignant breast cells.
ISSN:1538-4047
1555-8576
DOI:10.1080/15384047.2020.1750297