We found that MT2A overexpression or silencing can also modulate osteosarcoma cell sensitivity to these compounds.
Although blocking transcription using actinomycin D does not modulate PC3 cell sensitivity to IP6, inhibition of protein translation using cycloheximide has a significant protective effect.
Figure 3A shows that continuous treatment with actinomycin D, starting 4 h before the addition of IP6 (for 24 h), did not modulate PC3 cell sensitivity to IP6.
Although these results altogether suggest that the NF- κB classical pathway may be triggered in response to treatment of PC3 cells with IP6, inhibiting NF- κB transcriptional activity (assessed by κB-luc assay, Figure 1B), by transfecting PC3 cells with a non-degradable DN form of I κB- α (Brown et al, 1995), does not modulate PC3 cell sensitivity to IP6.
Different reports have identified miR-335 as a prognostic indicator in gastric cancer [ 73] and gliomas [ 74], whereas the overexpressed miR-181a has been reported to modulate T cell sensitivity and selection [ 75] and to contribute to human myeloid leukemia [ 76].
Recent studies suggest a function of microtubule-interacting proteins in modulating cancer cell sensitivity to microtubule-targeting drugs, although the precise molecular mechanisms remain elusive (Mohan et al., 2013; Rouzier et al., 2005; Sun et al., 2012; Veitia et al., 2000; Wagner et al., 2005; Wang et al., 2009).
Importantly, we also found that GSK-3 modulates MM cell sensitivity to BZ-induced apoptosis.
Altogether, these findings indicate that not only caspase-8, but also caspase-10 levels need to be tightly controlled, and that caspase-10 downregulation is likely to significantly influence and modulate NB cells sensitivity to DR-induced apoptosis.
In this plot these genes are displaced along the y-axis and encode proteins whose reduced expression modulates the cells' sensitivity to ISRIB.
