JUN activation modulates chromatin accessibility to drive TNFα-induced mesenchymal transition in glioblastoma.

Chromatin dynamics as well as genetic evolution underlies the adaptability of tumour cells to environmental cues. Three subtypes of tumour cells have been identified in glioblastoma, one of the commonest malignant brain tumours in adults. During tumour progression or under therapeutic pressure, the non-mesenchymal subtypes may progress to the mesenchymal subtype, leading to unfavourable prognosis. However, the molecular mechanisms for this transition remain poorly understood. Here taking a TNFα-induced cellular model, we profile the chromatin accessibility dynamics during mesenchymal transition. Moreover, we identify the JUN family as one of the key driving transcription factors for the gained chromatin accessibility. Accordingly, inhibition of JUN phosphorylation and therefore its transcription activity successfully impedes TNFα-induced chromatin remodelling and mesenchymal transition. In line with these findings based on experimental models, JUN activity is positively correlated with mesenchymal features in clinical glioblastoma specimens. Together, this study unveils a deregulated transcription regulatory network in glioblastoma progression and hopefully provides a rationale for anti-glioblastoma therapy.