Notch signalling antibodies and the jagged edge of cancer research

An extensive antibody catalog exists for the Notch signaling pathway. Notch proteins play an essential role in embryonic development and cell-signaling, with antibody studies showing them to be critical to apoptosis, vasculogenesis, hematopoiesis, myogenesis, morphogenesis and T-cell development. The Notch pathway has also been implicated in various types of cancer.

Antibody studies have identified Notch proteins to have a dual role, acting as both transcription factors, and as membrane receptors for Delta and Jagged ligands. Recently, scientists working with Notch signaling antibodies identified one of these ligands, Jagged2, as a promoter of metastasis in lung cancer. Jagged2 binds to the Notch2 receptor.

Ligand binding occurs at the Notch extracellular domain, resulting in a series of cleavages at the cytoplasmic domain. The Notch protein then translocates to the nucleus, triggering expression of Notch-responsive genes. Antibody research has indicated Notch signaling may be bi-directional, triggering events in the Jagged and Delta-expressing cells.

In a recent study using a mouse model for non-small cell (NSC) lung cancer, Kurie, Yang et al found that Jagged2/Notch2 binding can lead to silencing of miR-200. miR-200 is a microRNA thought to inhibit metastasis at the epithelial-to-mesenchymal transition stage.

The researchers first identified and isolated pro-metastatic NSC lung cancer cells, using CD133 marker antibodies. CD133 is virtually absent from primary lung tumors, but present in over 80% of the cell population of metastatic lesions. Over 50% of mice injected with CD133(+) cells developed metastatic cancer, compared to less than 20% of CD133(-) injected controls.

The CD133(+) cells showed marked overexpression of Notch ligands. In knock-down studies, cells depleted of Jagged2 failed to metastasize, while Jagged1 depletion had no effect. Further antibody experiments suggested Jagged2 inhibits miR-200 expression by regulating GATA3 expression. Studies have shown GATA3 and miR-200 counter-inhibit each other, and overexpression of GATA3 lowered miR-200 levels.

We at Novus Biologicals have an extensive antibody database covering all areas of the Notch signaling pathway.

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