Human NUMB6 Induces Epithelial-Mesenchymal Transition and Enhances Breast Cancer Cells Migration and Invasion.

Mammalian NUMB is alternatively spliced generating four isoforms NUMB1-NUMB4 that can function as tumor suppressors. NUMB1-NUMB4 proteins, which normally determine how different cell types develop, are reduced in 21% of primary breast tumors. Our previous work has, however, indicated that two novel NUMB isoforms, NUMB5 and NUMB6 have the pro-oncogenic functions.

A small peptide modeled after the NRAGE repeat domain inhibits XIAP-TAB1-TAK1 signaling for NF-κB activation and apoptosis in P19 cells.

In normal growth and development, apoptosis is necessary to shape the central nervous system and to eliminate excess neurons which are not required for innervation. In some diseases, however, apoptosis can be either overactive as in some neurodegenerative disorders or severely attenuated as in the spread of certain cancers. Bone morphogenetic proteins (BMPs) transmit signals for regulating cell growth, differentiation, and apoptosis.

Two novel human NUMB isoforms provide a potential link between development and cancer.

We previously identified four functionally distinct human NUMB isoforms. Here, we report the identification of two additional isoforms and propose a link between the expression of these isoforms and cancer. These novel isoforms, NUMB5 and NUMB6, lack exon 10 and are expressed in cells known for polarity and migratory behavior, such as human amniotic fluid cells, glioblastoma and metastatic tumor cells.

Mapping of NRAGE domains reveals clues to cell viability in BMP signaling.

Bone morphogenetic signaling (BMP) is a key pathway during neurogenesis and depends on many downstream intermediators to carry out its signaling. One such signaling pathway utilizes neurotrophin receptor-interacting MAGE protein (NRAGE), a member of the melanoma-associated antigen (MAGE) family, to upregulate p38 mitogen activated protein kinase (p38(MAPK)) in response to cellular stress and activate caspases which are critical in leading cells to death. NRAGE consists of two conserved MAGE homology domains separated by a unique hexapeptide repeat domain.

NRAGE: a potential rheostat during branching morphogenesis.

Branching morphogenesis is a developmental process characteristic of many organ systems. Specifically, during renal branching morphogenesis, its been postulated that the final number of nephrons formed is one key clinical factor in the development of hypertension in adulthood. As it has been established that BMPs regulate, in part, renal activity of p38 MAP kinase (p38(MAPK)) and it has demonstrated that the cytoplasmic protein Neurotrophin Receptor MAGE homologue (NRAGE) augments p38(MAPK) activation, it was hypothesized that a decrease in the expression of NRAGE during renal branching would result in decreased branching of the UB that correlated with changes in p38(MAPK) activation.

The use of Endo-Porter to deliver morpholinos in kidney organ culture.

Cellular interactions in development of the kidney are used as a model of reciprocal inductive events between epithelium and mesenchyme. Time- and labor-intensive methods have been developed to study this phenomenon. For example, in mice, the targeted disruption of genes in vivo has been used to modify the genetic program directing kidney development.