The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells.
RNAi-mediated blockade of AKT, HSF1 or HuR is sufficient to downregulate Rictor and inhibit GBM growth and invasive characteristics in vitro and suppress xenograft growth in mice.
When HSF1 or BIS knockdown was combined with temozolomide (TMZ) treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose) polymerase (PARP) cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased.
Here we show that ectopic expression of BAG3 in glioblastoma cells leads to the activation of an HSF1-driven stress response, as attested by transcriptional activation of BAG3 and Hsp70.