Aberrant Overexpression of Myosin 1b in Glioblastoma Promotes angiogenesis via VEGF-myc-myosin 1b- Piezo1 Axis

Abstract

Abstract Glioblastoma (GBM) is the most aggressive intracranial malignance with poor prognosis, which is attributed to the extreme invasiveness of the tumor. Enhanced angiogenesis is one of the essential hallmarks 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 was upregulated in GBM endothelial cells (ECs) compared to their paired non-malignant brain tissue. Knocking down myosin 1b in human/mouse brain endothelial cells inhibited EC migration, proliferation and tube formation. Myosin 1b in ECs are affected 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. Our results identified myosin 1b as a key mediator in promoting angiogenesis via Piezol1; suggested that VEGF/myc signaling pathway may be responsible for driving the changes of myosin 1b overexpression in GBM ECs.