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Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few...

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Autores principales: Li, Chen, Wang, Xiaolong, Chen, Tong, Li, Wenhao, Zhou, Xianyong, Wang, Lishui, Yang, Qifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243662/
https://www.ncbi.nlm.nih.gov/pubmed/35784473
http://dx.doi.org/10.3389/fcell.2022.913824
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author Li, Chen
Wang, Xiaolong
Chen, Tong
Li, Wenhao
Zhou, Xianyong
Wang, Lishui
Yang, Qifeng
author_facet Li, Chen
Wang, Xiaolong
Chen, Tong
Li, Wenhao
Zhou, Xianyong
Wang, Lishui
Yang, Qifeng
author_sort Li, Chen
collection PubMed
description Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few ICD-inducing agents are currently available. Here, we showed that Trametes robiniophila Murr (Huaier) triggered ICD in TNBC cells by promoting cell surface calreticulin (CRT) exposure, and increasing release of adenosine triphosphate (ATP) and high-mobility group protein B1 (HMGB1). Co-culturing with Huaier-treated TNBC cells efficiently enhanced the maturation of dendritic cells (DCs), which was further validated via cell-based vaccination assay. In the xenograft mouse model, oral administration of Huaier led to tumor-infiltrating lymphocytes (TILs) accumulation and significantly delayed tumor growth. Besides, depletion of endogenous T cells obviously abrogated the effect. Mechanically, Huaier could elicit endoplasmic reticulum (ER) stress-associated ICD through eIF2α signaling pathway. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity by binding with PKR in the cytoplasm and thus blocking its degradation. Taken together, we highlighted an essential role of circCLASP1/PKR/eIF2α axis in Huaier-induced ICD. The findings of our study carried significant translational potential that Huaier might serve as a promising option to achieve long-term tumor remission in patients with TNBC.
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spelling pubmed-92436622022-07-01 Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer Li, Chen Wang, Xiaolong Chen, Tong Li, Wenhao Zhou, Xianyong Wang, Lishui Yang, Qifeng Front Cell Dev Biol Cell and Developmental Biology Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few ICD-inducing agents are currently available. Here, we showed that Trametes robiniophila Murr (Huaier) triggered ICD in TNBC cells by promoting cell surface calreticulin (CRT) exposure, and increasing release of adenosine triphosphate (ATP) and high-mobility group protein B1 (HMGB1). Co-culturing with Huaier-treated TNBC cells efficiently enhanced the maturation of dendritic cells (DCs), which was further validated via cell-based vaccination assay. In the xenograft mouse model, oral administration of Huaier led to tumor-infiltrating lymphocytes (TILs) accumulation and significantly delayed tumor growth. Besides, depletion of endogenous T cells obviously abrogated the effect. Mechanically, Huaier could elicit endoplasmic reticulum (ER) stress-associated ICD through eIF2α signaling pathway. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity by binding with PKR in the cytoplasm and thus blocking its degradation. Taken together, we highlighted an essential role of circCLASP1/PKR/eIF2α axis in Huaier-induced ICD. The findings of our study carried significant translational potential that Huaier might serve as a promising option to achieve long-term tumor remission in patients with TNBC. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243662/ /pubmed/35784473 http://dx.doi.org/10.3389/fcell.2022.913824 Text en Copyright © 2022 Li, Wang, Chen, Li, Zhou, Wang and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Li, Chen
Wang, Xiaolong
Chen, Tong
Li, Wenhao
Zhou, Xianyong
Wang, Lishui
Yang, Qifeng
Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer
title Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer
title_full Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer
title_fullStr Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer
title_full_unstemmed Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer
title_short Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2α Signaling Pathway in Triple Negative Breast Cancer
title_sort huaier induces immunogenic cell death via circclasp1/pkr/eif2α signaling pathway in triple negative breast cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243662/
https://www.ncbi.nlm.nih.gov/pubmed/35784473
http://dx.doi.org/10.3389/fcell.2022.913824
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