PMID- 35784473
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 10
DP  - 2022
TI  - Huaier Induces Immunogenic Cell Death Via CircCLASP1/PKR/eIF2alpha Signaling Pathway 
      in Triple Negative Breast Cancer.
PG  - 913824
LID - 10.3389/fcell.2022.913824 [doi]
LID - 913824
AB  - 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 eIF2alpha 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/eIF2alpha 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.
CI  - Copyright (c) 2022 Li, Wang, Chen, Li, Zhou, Wang and Yang.
FAU - Li, Chen
AU  - Li C
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, China.
FAU - Wang, Xiaolong
AU  - Wang X
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, China.
FAU - Chen, Tong
AU  - Chen T
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, China.
FAU - Li, Wenhao
AU  - Li W
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, China.
FAU - Zhou, Xianyong
AU  - Zhou X
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, China.
FAU - Wang, Lishui
AU  - Wang L
AD  - Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
FAU - Yang, Qifeng
AU  - Yang Q
AD  - Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of 
      Medicine, Shandong University, Jinan, China.
AD  - Department of Pathology Tissue Bank, Qilu Hospital, Cheeloo College of Medicine, 
      Shandong University, Jinan, China.
AD  - Research Institute of Breast Cancer, Shandong University, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20220616
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC9243662
OTO - NOTNLM
OT  - Huaier
OT  - ICD
OT  - PKR
OT  - circRNA
OT  - er stress
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/06 06:00
MHDA- 2022/07/06 06:01
PMCR- 2022/01/01
CRDT- 2022/07/05 10:25
PHST- 2022/04/06 00:00 [received]
PHST- 2022/05/26 00:00 [accepted]
PHST- 2022/07/05 10:25 [entrez]
PHST- 2022/07/06 06:00 [pubmed]
PHST- 2022/07/06 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 913824 [pii]
AID - 10.3389/fcell.2022.913824 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2022 Jun 16;10:913824. doi: 10.3389/fcell.2022.913824. 
      eCollection 2022.