CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation.
A Kinase Anchor Proteins
/ metabolism
CD47 Antigen
/ metabolism
Cell Adhesion
/ physiology
Cell Line, Tumor
Guanine Nucleotide Exchange Factors
/ metabolism
Humans
Lymphoma, T-Cell
/ metabolism
Macrophages
/ metabolism
Minor Histocompatibility Antigens
/ metabolism
Neoplasm Metastasis
/ pathology
Phagocytosis
Proto-Oncogene Proteins
/ metabolism
Signal Transduction
/ physiology
Up-Regulation
/ physiology
rhoA GTP-Binding Protein
/ metabolism
Rho-GEF
TSP-1
integrin
phagocytosis
small-G protein
Journal
International immunology
ISSN: 1460-2377
Titre abrégé: Int Immunol
Pays: England
ID NLM: 8916182
Informations de publication
Date de publication:
22 04 2021
22 04 2021
Historique:
received:
09
09
2020
accepted:
06
01
2021
pubmed:
7
1
2021
medline:
4
2
2022
entrez:
6
1
2021
Statut:
ppublish
Résumé
CD47, a 50 kDa transmembrane protein, facilitates integrin-mediated cell adhesion and inhibits cell engulfment by phagocytes. Since CD47 blocking promotes engulfment of cancer cells by macrophages, it is important to clarify the mechanism of CD47 signaling in order to develop treatments for diseases involving CD47-overexpressing cancer cells, including breast cancer and lymphoma. Here, we show that CD47 plays an essential role in T-cell lymphoma metastasis by up-regulating basal RhoA activity independent of its anti-phagocytic function. CD47 interacts with AKAP13, a RhoA-specific guanine nucleotide exchange factor (GEF), and facilitates AKAP13-mediated RhoA activation. Our study shows that CD47 has a novel function on the AKAP13-RhoA axis and suggests that CD47-AKAP13 interaction would be a novel target for T-cell lymphoma treatment.
Identifiants
pubmed: 33406263
pii: 6066586
doi: 10.1093/intimm/dxab002
doi:
Substances chimiques
A Kinase Anchor Proteins
0
AKAP13 protein, human
0
CD47 Antigen
0
CD47 protein, human
0
Guanine Nucleotide Exchange Factors
0
Minor Histocompatibility Antigens
0
Proto-Oncogene Proteins
0
RHOA protein, human
124671-05-2
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
273-280Informations de copyright
© The Japanese Society for Immunology. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.