Notch signaling promotes a HIF2α-driven hypoxic response in multiple tumor cell types

Proline oxidase promotes tumor cell survival in hypoxic tumor microenvironments.

Proline is a readily released stress substrate that can be metabolized by proline oxidase (POX) to generate either reactive oxygen species (ROS) to induce apoptosis or autophagy or ATP during times of nutrient stress. However, the contribution of proline metabolism to tumorigenesis in hypoxic microenvironments has not been explored. In this study, we investigated the different functions of POX ...

JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation.

Several studies have revealed links between hypoxia and activation of Notch in solid tumors. While most reports have focused on intracellular domain of the Notch1 receptor (icN1) stabilization by direct interaction with HIF proteins, little attention has been given to Notch ligand regulation during hypoxia. Here we show that the Notch ligand JAG2 is transcriptionally activated by hypoxia in a H...

Tumor and Stem Cell Biology Proline Oxidase Promotes Tumor Cell Survival in Hypoxic Tumor Microenvironments

Proline is a readily released stress substrate that can bemetabolized by proline oxidase (POX) to generate either reactive oxygen species (ROS) to induce apoptosis or autophagy or ATP during times of nutrient stress. However, the contribution of prolinemetabolism to tumorigenesis in hypoxicmicroenvironments has not been explored. In this study, we investigated the different functions of POX und...

Angiogenesis in Response to Hypoxic Promotes Tumor Cell Adaptation and Perk-Dependent Translational Regulation

Impaired notch signaling promotes de novo squamous cell carcinoma formation.

Signaling through Notch receptors in the skin has been implicated in the differentiation, proliferation, and survival of keratinocytes, as well as in the pathogenesis of basal cell carcinoma (BCC). To determine the composite function of Notch receptor-mediated signaling in the skin and overcome potential redundancies between receptors, conditional transgenic mice were generated that express the...