1. Academic Validation
  2. Activin A, a Novel Chemokine, Induces Mouse NK Cell Migration via AKT and Calcium Signaling

Activin A, a Novel Chemokine, Induces Mouse NK Cell Migration via AKT and Calcium Signaling

  • Cells. 2024 Apr 23;13(9):728. doi: 10.3390/cells13090728.
Yunfeng Wang 1 2 Zhonghui Liu 1 2 Yan Qi 1 2 Jiandong Wu 3 Boyang Liu 4 5 Xueling Cui 2 4
Affiliations

Affiliations

  • 1 Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
  • 2 Key Laboratory of Neuroimmunology and Clinical Immunology, Changchun 130021, China.
  • 3 Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
  • 4 Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
  • 5 Department of Scientific Research, Jilin Jianzhu University, Changchun 130118, China.
Abstract

Natural killer (NK) cells can migrate quickly to the tumor site to exert cytotoxic effects on tumors, and some chemokines, including CXCL8, CXCL10 or and CXCL12, can regulate the migration of NK cells. Activin A, a member of the transforming growth factor β (TGF-β) superfamily, is highly expressed in tumor tissues and involved in tumor development and immune cell activation. In this study, we focus on the effects of Activin A on NK cell migration. In vitro, Activin A induced NK cell migration and invasion, promoted cell polarization and inhibited cell adhesion. Moreover, Activin A increased CA2+, p-SMAD3 and p-AKT levels in NK cells. An Akt Inhibitor and CA2+ chelator partially blocked activin A-induced NK cell migration. In vivo, exogenous Activin A increased tumor-infiltrating NK cells in NS-1 cell solid tumors and inhibited tumor growth, and blocking endogenous Activin A with anti-activin A antibody reduced tumor-infiltrating NK cells in 4T-1 cell solid tumors. These results suggest that Activin A induces NK cell migration through Akt signaling and calcium signaling and may enhance the antitumor effect of NK cells by increasing tumor-infiltrating NK cells.

Keywords

AKT signaling; activin A; calcium signaling; migration; natural killer cells.

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