| First Author | Tormo D | Year | 2009 |
| Journal | Cancer Cell | Volume | 16 |
| Issue | 2 | Pages | 103-14 |
| PubMed ID | 19647221 | Mgi Jnum | J:151975 |
| Mgi Id | MGI:4355645 | Doi | 10.1016/j.ccr.2009.07.004 |
| Citation | Tormo D, et al. (2009) Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer Cell 16(2):103-14 |
| abstractText | Inappropriate drug delivery, secondary toxicities, and persistent chemo- and immunoresistance have traditionally compromised treatment response in melanoma. Using cellular systems and genetically engineered mouse models, we show that melanoma cells retain an innate ability to recognize cytosolic double-stranded RNA (dsRNA) and mount persistent stress response programs able to block tumor growth, even in highly immunosuppressed backgrounds. The dsRNA mimic polyinosine-polycytidylic acid, coadministered with polyethyleneimine as carrier, was identified as an unanticipated inducer of autophagy downstream of an exacerbated endosomal maturation program. A concurrent activity of the dsRNA helicase MDA-5 driving the proapoptotic protein NOXA resulted in an efficient autodigestion of melanoma cells. These results reveal tractable links for therapeutic intervention among dsRNA helicases, endo/lysosomes, and apoptotic factors. |
