PMID- 37845206
OWN - NLM
STAT- MEDLINE
DCOM- 20231025
LR  - 20231107
IS  - 2041-4889 (Electronic)
VI  - 14
IP  - 10
DP  - 2023 Oct 16
TI  - LAIR1 drives glioma progression by nuclear focal adhesion kinase dependent 
      expressions of cyclin D1 and immunosuppressive chemokines/cytokines.
PG  - 684
LID - 10.1038/s41419-023-06199-9 [doi]
LID - 684
AB  - Leukocyte-associated immunoglobulin-like receptor-1 (LAIR1), an immune receptor 
      containing immunoreceptor tyrosine-based inhibiory motifs (ITIMs), has emerged as 
      an attractive target for cancer therapy. However, the intrinsic function of LAIR1 
      in gliomas remains unclear. In this study, the poor prognosis of glioma patients 
      and the malignant proliferation of glioma cells in vitro and in vivo were found 
      to be closely correlated with LAIR1. LAIR1 facilitates focal adhesion kinase 
      (FAK) nuclear localization, resulting in increased transcription of cyclin D1 and 
      chemokines/cytokines (CCL5, TGFbeta2, and IL33). LAIR1 specifically supports in the 
      immunosuppressive glioma microenvironment via CCL5-mediated microglia/macrophage 
      polarization. SHP2(Q510E) (PTP domain mutant) or FAK(NLM) (non-nuclear localizing 
      mutant) significantly reversed the LAIR1-induced growth enhancement in glioma 
      cells. In addition, LAIR1(Y251/281F) (ITIMs mutant) and SHP2(Q510E) mutants 
      significantly reduced FAK nuclear localization, as well as CCL5 and cyclin D1 
      expression. Further experiments revealed that the ITIMs of LAIR1 recruited 
      SH2-containing phosphatase 2 (SHP2), which then interacted with FAK and induced 
      FAK nuclear localization. This study uncovered a critical role for intrinsic 
      LAIR1 in facilitating glioma malignant progression and demonstrated a requirement 
      for LAIR1 and SHP2 to enhance FAK nuclear localization.
CI  - (c) 2023. The Author(s).
FAU - Wei, Xiaoqian
AU  - Wei X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Pan, Shushan
AU  - Pan S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Wang, Zirui
AU  - Wang Z
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Chen, Jieru
AU  - Chen J
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Lu, Li
AU  - Lu L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Cao, Qizhi
AU  - Cao Q
AD  - Department of Immunology, School of Basic Medical Sciences, Binzhou Medical 
      University, Yantai, Shandong, 264003, P.R. China.
FAU - Song, Shuling
AU  - Song S
AD  - School of Gerontology, Binzhou Medical University, Yantai, 264003, Shandong, P.R. 
      China.
FAU - Zhang, Huachang
AU  - Zhang H
AD  - Department of Immunology, School of Basic Medical Sciences, Binzhou Medical 
      University, Yantai, Shandong, 264003, P.R. China.
FAU - Liu, Xiaohui
AU  - Liu X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Qu, Xianjun
AU  - Qu X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China.
FAU - Lin, Xiukun
AU  - Lin X
AD  - College of Marine Sciences, Beibu Gulf University, Qinzhou, 535011, Guangxi, P.R. 
      China.
FAU - Xu, Huanli
AU  - Xu H
AUID- ORCID: 0000-0002-4599-9271
AD  - Department of Pharmacology, School of Basic Medical Sciences, Capital Medical 
      University, Beijing, P.R. China. xuhuanli@ccmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231016
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Chemokines)
RN  - 136601-57-5 (Cyclin D1)
RN  - 0 (Cytokines)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - 0 (leukocyte-associated immunoglobulin-like receptor 1)
RN  - 0 (CCND1 protein, human)
SB  - IM
MH  - Humans
MH  - Chemokines
MH  - Cyclin D1/genetics/metabolism
MH  - *Cytokines
MH  - Focal Adhesion Kinase 1/genetics/metabolism
MH  - Focal Adhesion Protein-Tyrosine Kinases/metabolism
MH  - *Glioma/genetics
MH  - Tumor Microenvironment
PMC - PMC10579300
COIS- The authors declare no competing interests.
EDAT- 2023/10/17 00:42
MHDA- 2023/10/23 01:18
PMCR- 2023/10/16
CRDT- 2023/10/16 23:16
PHST- 2023/05/22 00:00 [received]
PHST- 2023/09/28 00:00 [accepted]
PHST- 2023/09/19 00:00 [revised]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/10/17 00:42 [pubmed]
PHST- 2023/10/16 23:16 [entrez]
PHST- 2023/10/16 00:00 [pmc-release]
AID - 10.1038/s41419-023-06199-9 [pii]
AID - 6199 [pii]
AID - 10.1038/s41419-023-06199-9 [doi]
PST - epublish
SO  - Cell Death Dis. 2023 Oct 16;14(10):684. doi: 10.1038/s41419-023-06199-9.