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

Olena Odnokoz; Pengfei Yu; Amy R. Peck; Yunguang Sun; Albert J. Kovatich; Jeffrey A. Hooke; Hai Hu; Edith P. Mitchell; Hallgeir Rui; Serge Y. Fuchs

doi:10.1080/15384047.2020.1750297

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

Olena Odnokoz, Pengfei Yu, Amy R. Peck, Yunguang Sun, Albert J. Kovatich, Jeffrey A. Hooke, Hai Hu, Edith P. Mitchell, Hallgeir Rui, Serge Y. Fuchs^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	629-636
Number of pages	8
Journal	Cancer Biology and Therapy
Volume	21
Issue number	7
DOIs	https://doi.org/10.1080/15384047.2020.1750297
State	Published - 2 Jul 2020
Externally published	Yes

Keywords

IFNAR1
PD-L1
breast cancer
immune therapy
interferon receptor
mammary adenocarcinoma
type I interferon

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10.1080/15384047.2020.1750297

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title = "Malignant cell-specific pro-tumorigenic role of type I interferon receptor in breast cancers",

abstract = "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 IFNAR1S526A 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.",

keywords = "IFNAR1, PD-L1, breast cancer, immune therapy, interferon receptor, mammary adenocarcinoma, type I interferon",

author = "Olena Odnokoz and Pengfei Yu and Peck, {Amy R.} and Yunguang Sun and Kovatich, {Albert J.} and Hooke, {Jeffrey A.} and Hai Hu and Mitchell, {Edith P.} and Hallgeir Rui and Fuchs, {Serge Y.}",

note = "Publisher Copyright: {\textcopyright} 2020, {\textcopyright} 2020 Taylor & Francis Group, LLC.",

year = "2020",

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doi = "10.1080/15384047.2020.1750297",

language = "English",

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AU - Odnokoz, Olena

AU - Yu, Pengfei

AU - Peck, Amy R.

AU - Sun, Yunguang

AU - Kovatich, Albert J.

AU - Hooke, Jeffrey A.

AU - Hu, Hai

AU - Mitchell, Edith P.

AU - Rui, Hallgeir

AU - Fuchs, Serge Y.

PY - 2020/7/2

Y1 - 2020/7/2

N2 - 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 IFNAR1S526A 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.

AB - 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 IFNAR1S526A 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.

KW - IFNAR1

KW - PD-L1

KW - breast cancer

KW - immune therapy

KW - interferon receptor

KW - mammary adenocarcinoma

KW - type I interferon

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DO - 10.1080/15384047.2020.1750297

M3 - Article

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AN - SCOPUS:85084376942

SN - 1538-4047

VL - 21

SP - 629

EP - 636

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

IS - 7

ER -

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

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Keywords

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