| First Author | Jeong JH | Year | 2017 |
| Journal | Mol Cell | Volume | 65 |
| Issue | 1 | Pages | 154-167 |
| PubMed ID | 28041912 | Mgi Jnum | J:249193 |
| Mgi Id | MGI:6094322 | Doi | 10.1016/j.molcel.2016.11.034 |
| Citation | Jeong JH, et al. (2017) A Constitutive Intrinsic Inflammatory Signaling Circuit Composed of miR-196b, Meis2, PPP3CC, and p65 Drives Prostate Cancer Castration Resistance. Mol Cell 65(1):154-167 |
| abstractText | Androgen deprivation therapy is the most effective treatment for advanced prostate cancer, but almost all cancer eventually becomes castration resistant, and the underlying mechanisms are largely unknown. Here, we show that an intrinsic constitutively activated feedforward signaling circuit composed of IkappaBalpha/NF-kappaB(p65), miR-196b-3p, Meis2, and PPP3CC is formed during the emergence of castration-resistant prostate cancer (CRPC). This circuit controls the expression of stem cell transcription factors that drives the high tumorigenicity of CRPC cells. Interrupting the circuit by targeting its individual components significantly impairs the tumorigenicity and CRPC development. Notably, constitutive activation of IkappaBalpha/NF-kappaB(p65) in this circuit is not dependent on the activation of traditional IKKbeta/NF-kappaB pathways that are important in normal immune responses. Therefore, our studies present deep insight into the bona fide mechanisms underlying castration resistance and provide the foundation for the development of CRPC therapeutic strategies that would be highly efficient while avoiding indiscriminate IKK/NF-kappaB inhibition in normal cells. |
