MPZL1 as an HGF/MET signaling amplifier promotes cell migration and invasion in glioblastoma

The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely low.We,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.

Single-cell analyses identify anaphase-promoting complex subunit 11 as a switch controlling neuronal differentiation of glioblastoma cells

Glioblastoma(GBM)is the most common and lethal malignancy in the central nervous system.1 One of the major difficulties in treatment is that the initial clinical diagnosis of GBM is already WHO grade IV,without recognizable lower-grade precursor lesions.Copy number variations(CNVs)were found to appear in malignant cells several years before the initial diagnosis of GBM.2 Less differentiation and more aggressive phenotypes were observed in GBM cells with a higher degree of CNVs.3 Additionally,CNVs provide more accurate stratification of clinical outcomes than does the WHO grade system.4 Therefore,we reasoned that differentially expressed genes(DEGs)among GBM cells with different CNV statuses would be significant for the aggressiveness of GBM.Here we leveraged the single-cell RNA-sequencing(scRNA-seq)to construct the CNV profile of GBM at single-cell resolution,divided GBM cells into different clusters according to their CNV statuses,and investigated the molecular functions of DEGs among GBM clusters.Through a series of experiments,we identified anaphase-promoting complex subunit 11(ANAPC11)as a switch controlling the neuronal differentiation of GBM cells,providing a novel alternative for the development of differentiation-inducing therapy to overcome GBM.