Abstract IA10: Notch signaling and cancer

Cancer can be seen as disease of perturbed self-renewal. In the last decades it became clear that many of the signaling pathways known to be important during embryonic development also play important roles in regulating self-renewing tissues. Deregulation of the self-renewal process results in sustained proliferation, evasion of cell death, loss of differentiation capacity, invasion and metastasis all of which are hallmarks of cancer. The major question is how do these deregulated signaling cascades mechanistically contribute to cancer and are they suitable for targeting therapy?The Notch pathway is one such cascade required for normal stem cell maintenance and development of different organs. Over activation of this pathway due to mutations in the Notch receptor are found in more than 50% of human T-cell leukemia and deregulated Notch signaling has been shown to promote tumor progression of various organs. The oncogenic mediators of aberrant Notch function in T-ALL and other Notch-driven cancers appear to be manifold and complex. The modulatory function of individual miRNAs in Notch driven T-ALLs has recently been established. However, whether Dicer1-processed miRNAs are essential for Notch-driven T-ALL is currently unknown. We used conditional and inducible genetic loss of function approaches to show that development and maintenance of Notch-driven T-ALL is dependent on Dicer1 function. Lineage tracing experiments revealed that Dicer1 deficiency led to the induction of apop...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways: Notch: Oral Presentations - Invited Abstracts Source Type: research