Aberrant overexpression of myosin 1b in glioblastoma promotes angiogenesis via VEGF-myc-myosin 1b-Piezo1 axis

Weifeng Lv; Fan Yang; Zhengmao Ge; Lele Xin; Lingxue Zhang; Yaohong Zhai; Xian Liu; Qingdong Guo; Xinggang Mao; Peng Luo; Lei Zhang; Xiaofan Jiang; Yanyu Zhang

doi:10.1016/j.jbc.2024.107807

Aberrant overexpression of myosin 1b in glioblastoma promotes angiogenesis via VEGF-myc-myosin 1b-Piezo1 axis

J Biol Chem. 2024 Sep 20:107807. doi: 10.1016/j.jbc.2024.107807. Online ahead of print.

Authors

Weifeng Lv¹, Fan Yang², Zhengmao Ge¹, Lele Xin³, Lingxue Zhang³, Yaohong Zhai³, Xian Liu³, Qingdong Guo¹, Xinggang Mao¹, Peng Luo¹, Lei Zhang³, Xiaofan Jiang⁴, Yanyu Zhang⁵

Affiliations

¹ Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
² Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Rudbeck Laboratory, 75185, Uppsala, Sweden; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neuro-injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
³ China-Sweden International Joint Research Center for Brain Diseases, College of Life Sciences, Shaanxi Normal University, Xi'an 710119, China.
⁴ Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: jiangxf@fmmu.edu.cn.
⁵ Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China. Electronic address: yanyu.zhang@fmmu.edu.cn.

PMID: 39307302
DOI: 10.1016/j.jbc.2024.107807

Abstract

Glioblastoma (GBM) is the most aggressive intracranial malignancy with poor prognosis. Enhanced angiogenesis is an essential hallmark of GBM, which demonstrates extensive microvascular proliferation and abnormal vasculature. Here, we uncovered the key role of myosin 1b in angiogenesis and vascular abnormality in GBM. Myosin 1b is upregulated in GBM endothelial cells (ECs) compared to the paired non-malignant brain tissue. In our study, we found that myosin 1b promotes migration, proliferation and angiogenesis of human/mouse brain ECs. We also found that myosin 1b expression in ECs can be regulated by vascular endothelial growth factor (VEGF) signaling through myc. Moreover, myosin 1b promotes angiogenesis via Piezo1 by enhancing Ca²⁺ influx, in which process VEGF can be the trigger. In conclusion, our results identified myosin 1b as a key mediator in promoting angiogenesis via mechanosensitive ion channel component 1 (Piezo1) and suggested that VEGF/myc signaling pathway could be responsible for driving the changes of myosin 1b overexpression in GBM ECs.

Keywords: Myc; Piezo1; VEGF; calcium channel; glioblastoma; myosin 1b; tumor vessel.