BACKGROUND: It is well-known that glioblastoma contains self-renewing, stem-like 
subpopulation with the ability to sustain tumor growth. These cells - called 
cancer stem-like cells - share certain phenotypic characteristics with 
untransformed stem cells and are resistant to many conventional cancer 
therapies, which might explain the limitations in curing human malignancies. 
Thus, the identification of genes controlling the differentiation of these 
stem-like cells is becoming a successful therapeutic strategy, owing to the 
promise of novel targets for treating malignancies.
METHODS: Recently, we developed SWIM, a software able to unveil a small pool of 
genes - called switch genes - critically associated with drastic changes in cell 
phenotype. Here, we applied SWIM to the expression profiling of glioblastoma 
stem-like cells and conventional glioma cell lines, in order to identify switch 
genes related to stem-like phenotype.
RESULTS: SWIM identifies 171 switch genes that are all down-regulated in 
glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, 
COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in 
"ECM-receptor interaction" and "focal adhesion" pathways. The inhibition of 
switch genes highly correlates with the activation of genes related to neural 
development and differentiation, such as the 4-core OLIG2, POU3F2, SALL2, SOX2, 
whose induction has been shown to be sufficient to reprogram differentiated 
glioblastoma into stem-like cells. Among switch genes, the transcription factor 
FOSL1 appears as the brightest star since: it is down-regulated in stem-like 
cells; it highly negatively correlates with the 4-core genes that are all 
up-regulated in stem-like cells; the promoter regions of the 4-core genes harbor 
a consensus binding motif for FOSL1.
CONCLUSIONS: We suggest that the inhibition of switch genes in stem-like cells 
could induce the deregulation of cell communication pathways, contributing to 
neoplastic progression and tumor invasiveness. Conversely, their activation 
could restore the physiological equilibrium between cell adhesion and migration, 
hampering the progression of cancer. Moreover, we posit FOSL1 as promising 
candidate to orchestrate the differentiation of cancer stem-like cells by 
repressing the 4-core genes' expression, which severely halts cancer growth and 
might affect the therapeutic outcome. We suggest FOSL1 as novel putative 
therapeutic and prognostic biomarker, worthy of further investigation.