A TRIP230-retinoblastoma protein complex regulates hypoxia-inducible factor-1α-mediated transcription and cancer cell invasion.

ABSTRACT: Localized hypoxia in solid tumors activates transcriptional programs that promote the metastatic transformation of cells. Like hypoxia-inducible hyper-vascularization, loss of the retinoblastoma protein (Rb) is a trait common to advanced stages of tumor progression in many metastatic cancers. However, no link between the role of Rb and hypoxia-driven metastatic processes has been established. We demonstrated that Rb is a key mediator of the hypoxic response mediated by HIF1α/β, the master regulator of the hypoxia response, and its essential co-activator, the thyroid hormone receptor/retinoblastoma-interacting protein (TRIP230). Furthermore, loss of Rb unmasks the full co-activation potential of TRIP230. Using small inhibitory RNA approaches in vivo, we established that Rb attenuates the no

SUBMITTER: Labrecque MP 

PROVIDER: S-EPMC4053355 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature