Molecular cross-talk between the TRAIL and interferon signaling pathways.


TRAIL/APO-2L induces apoptosis in a variety of transformed cells and has potential as an anti-cancer therapeutic. The physiologic role of TRAIL is presumably more complex than merely activating caspase-mediated cell death. To shed light into TRAIL-mediated signaling, we used DNA microarrays to profile gene expression mediated by TRAIL in breast carcinoma cells. Primary response genes induced by TRAIL included a number of known NF-kappaB-dependent genes such as cIAP2, A20, and E-selectin. Remarkably, global transcriptome analysis revealed that TRAIL also induced a cohort of genes related to the interferon-signaling pathway. Assessing interferon-induced gene expression suggested various points of interaction with the TRAIL signaling pathway. Interestingly, while we observed interferon-mediated up-regulation of TRAIL, we also demonstrated a concomitant TRAIL-mediated induction of interferon-beta. Combining TRAIL and interferon in vitro, synergistically induced apoptosis and caspase activation in breast cancer cells. Together, these data indicate multiple levels of molecular cross-talk between the two diverse cytokines with anti-tumor properties.

Extracted Key Phrases

8 Figures and Tables

Citations per Year

419 Citations

Semantic Scholar estimates that this publication has 419 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{KumarSinha2002MolecularCB, title={Molecular cross-talk between the TRAIL and interferon signaling pathways.}, author={Chandan Kumar-Sinha and Sooryanarayana Varambally and Arun Sreekumar and Arul M. Chinnaiyan}, journal={The Journal of biological chemistry}, year={2002}, volume={277 1}, pages={575-85} }