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The Snail-Induced Sulfonation Pathway in Breast Cancer Metastasis
Final rept. 1 Jul 2011-30 Jun 2014
WISTAR INST OF ANATOMY AND BIOLOGY PHILADELPHIA PA
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This support from DOD has provided funding for a 3-year project that has resulted in fundamental new insights into how the transcription factor Snail can control gene regulation processes that regulate cancer metastases. The new discoveries include 1. Binding of Snail to PRKG1, 14-3-3 and RING1aB proteins 2. Derivation of a model for Snail-DNA interaction and its verification using mutagenesis 3. Phosphorylation of Snail by the kinase PRKG1 and recruitment of PO4-Snail to target genes 4. Demonstration that LIMD2 is in the EMT pathway and also contributes to cancer metastases by regulating EMT, likely thru Snail pathways. Many of these have been published or are in preparation for publication. The demonstration that the PAPSS1 and PAPSS2 genes are direct targets for Snail during EMT continues to be elusive, mostly for technical reasons. Overall, this support has resulted in the discovery of key novel principles in EMT mediated gene regulation and has provided new exploitable targets for metastasis prevention and therapeutics which will be followed up in further studies which are ongoing.
APPROVED FOR PUBLIC RELEASE