2. Academic Validation
  3. Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis

Nuclear translocation of cGAS orchestrates VEGF-A-mediated angiogenesis

  • Cell Rep. 2023 Apr 5;42(4):112328. doi: 10.1016/j.celrep.2023.112328.
Juanjuan Luo 1,  Chunjiao Lu 1,  Yang Chen 1,  Xuewei Wu 1,  Chenchen Zhu 1,  Wei Cui 2,  Shicang Yu 3,  Ningning Li 4,  Yihang Pan 4,  Weijiang Zhao 5,  Qingkai Yang 6,  Xiaojun Yang 7
Affiliations

Affiliations

  • 1 Shantou University Medical College, Shantou, Guangdong 515041, China.
  • 2 College of Life Science and Biopharmaceutical of Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
  • 3 Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
  • 4 The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, China.
  • 5 Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China.
  • 6 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, China. Electronic address: yangqingkai@dmu.edu.cn.
  • 7 Shantou University Medical College, Shantou, Guangdong 515041, China. Electronic address: yangx@stu.edu.cn.
PMID: 37027305 DOI: 10.1016/j.celrep.2023.112328
Abstract

Cyclic GMP-AMP Synthase (cGAS) senses cytosolic incoming DNA and consequently activates stimulator of interferon response cGAMP interactor 1 (STING) to mount immune response. Here, we show nuclear cGAS could regulate VEGF-A-mediated angiogenesis in an immune-independent manner. We found VEGF-A stimulation induces cGAS nuclear translocation via importin-β pathway. Moreover, nuclear cGAS subsequently regulates miR-212-5p-ARPC3 cascade to modulate VEGF-A-mediated angiogenesis through affecting cytoskeletal dynamics and VEGFR2/KDR/Flk-1 trafficking from trans-Golgi network (TGN) to plasma membrane via a regulatory feedback loop. In contrast, cGAS deficiency remarkably impairs VEGF-A-mediated angiogenesis in vivo and in vitro. Furthermore, we found strong association between the expression of nuclear cGAS and VEGF-A, and the malignancy and prognosis in malignant glioma, suggesting that nuclear cGAS might play important roles in human pathology. Collectively, our findings illustrated the function of cGAS in angiogenesis other than immune surveillance, which might be a potential therapeutic target for pathological angiogenesis-related diseases.

Keywords

ARPC3; CP: Cell biology; VEGF-A; VEGFR2; angiogenesis; cGAS; zebrafish.

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