It has various subtypes transitions depending upon the molecular features among which mesenchymal transition is the most frequent one.
‘Master regulator gene FOSL1 is found to serve as a general genetic switch for the mesenchymal subtype of glioblastoma, which is associated with the poorest prognosis of brain cancer.’
Another gene – NF1 had also been known to play a prime role in mesenchymal glioblastoma. However, its mechanism was unknown. The scientists have now uncovered that the “missing link” between NF1 and the activation of the genetic program involved in mesenchymal glioblastoma is FOSL1.
Even if this finding might not be translated into a novel treatment in the short or medium term, “it is a big step forward in the search for therapies for this type of cancer with poor prognosis” says Massimo Squatrito, Head of The Seve-Ballesteros Foundation Brain Tumour Group and main co-author of the study.
The team found that in the mice model lacking the master regulator gene FOSL1 (despite mutations in NF1) resulted in the delayed tumor development. Moreover, the cancer stem cells (tumorigenic cells) actually lost their capabilities of self-renewal and regeneration.
The study shows that FOSL1 plays a fundamental role. “Our data indicate that FOSL1 is a key regulator of both glioblastoma plasticity and mesenchymal transition,” says the authors.
The team further anticipates developing ways for blocking this gene to serve as a therapeutic intervention.