DAP5/eIF3d: A new translation initiation mechanism that is essential for breast cancer metastasis

Tidsperiod: 2021-01-01 till 2023-12-31

Projektledare: Varsha Prakash

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 3 150 000 SEK

Currently there are no effective treatments that can cure metastatic breast cancer and therefore patients diagnosed with metastatic disease have an extremely poor prognosis. A critical program underlying the metastatic spread of cancer is the Epithelial-to-Mesenchymal Transition (EMT). A better understanding of the EMT program is therefore needed, as such knowledge will expand the repertoire of potential novel therapies targeting metastasis. The goal of my study is to investigate a newly discovered alternative cap-dependent DAP5/eIF3d-mediated mRNA translation program and its role in EMT, breast cancer development and metastasis. In these studies, I will compare the effect of silencing or overexpression of DAP5 or eIF4E/eIF4GI in human and murine breast cancer cell lines. I will also investigate the effect of DAP5 on translational control of primary tumor development, progression and metastasis in two animal models. Further, I will employ state of the art technology including ribosome foot printing to determine genome wide changes in translation regulation by DAP5. These studies will provide unique insights into the central role of alternative cap-dependent translational control by the DAP5/eIF3d complex in EMT and metastasis in breast cancer. These mechanistic studies would ultimately inform on how to develop novel pharmacologic inhibitors targeting DAP5/eIF3d to prevent or treat breast cancer metastasis.