Translational regulation is critical in cancer development and progression. Translation sustains tumor growth and development of a tumor vasculature, a process known as angiogenesis, which is activated by hypoxia. Here we first demonstrate that a majority of large advanced breast cancers overexpress translation regulatory protein 4E-BP1 and initiation factor eIF4G. Using model animal and cell studies, we then show that overexpressed 4E-BP1 and eIF4G orchestrate a hypoxia-activated switch from cap-dependent to cap-independent mRNA translation that promotes increased tumor angiogenesis and growth at the level of selective mRNA translation. Elevated levels of 4E-BP1 trigger hypoxia inhibition of cap-dependent mRNA translation at high-oxygen levels and, with eIF4G, increase selective translation of mRNAs containing internal ribosome entry sites (IRESs) that include key proangiogenic, hypoxia, and survival mRNAs. The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models.

Stufenweise einstellbar ist die Leitfähigkeit in einer Reihe aus acht Biphenyldithiolen mit festgelegten Torsionswinkeln zwischen den Arenebenen, die synthetisiert und in einem STM‐Einzelmolekülbruchkontakt untersucht wurden. Dabei ergab sich eine cos2‐Abhängigkeit zwischen dem Torsionswinkel und der Leitfähigkeit der einzelnen Moleküle (siehe Diagramm).

The results strongly suggest that papillary lesions diagnosed as benign at core-needle biopsy should be surgically excised because a substantial number of lesions were upgraded to ADH and DCIS at excision.

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