Fra-1 stimulates and PTPL1 inhibits proliferation and invasion of breast cancer cells suggesting an active role of both proteins in tumor aggressiveness. Indeed, Fra-1 is overexpressed in triple negative breast cancer cells (ER-, PR-, Erb2-) whereas PTPL1 expression is low in ER- cell lines and tumors. Moreover, our recent results suggest that Fra-1 phosphorylation is necessary to its biological and transcriptional activities and that PTPL1 activity can be regulated by tyrosine phosphorylation.
Our current projects are therefore:
• To precise how phosphorylations regulate PTPL1 and Fra-1 expression and\or activity which might ultimately lead to the proposition of new therapies based on kinase inhibitors.
• To determine by large scale methods the targets of both proteins (Substrate Trapping + iTRAQ and mass spectrophotometry for PTPL1; ChIP-SEQ for Fra-1) and thus potentially identify new therapeutic targets.
In parallel with these fundamental approaches, translational studies aim to validate our results will be develop in particular in triple negative cancer.
In addition, for the last years, M. Garcia and P Nirdé, in collaboration with chemists and physicists, have developed a new thematic concerning the improvement and use of glycovectors in the aim to define new therapies based on the targeting of the mannose-6 phosphate membrane receptor in lysosomial diseases and cancer.
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