When the non-coding codes: Mining the microproteome for novel regulators of cancer cell plasticity

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• Dr Maria Abad from Altos Labs, Cambridge
• Thursday 08 February 2024, 13:00-14:00
• Biffen Lecture theatre and Zoom.

If you have a question about this talk, please contact Caroline Newnham.

Host - Steve Russell

My group is focused on the discovery of microproteins relevant for cellular plasticity and cancer. Using a computational method for phylogenetic analysis, we have identified 5 novel and evolutionary conserved microproteins dysregulated in cancer and in cellular differentiation/de-differentiation processes. We have experimentally validated their translation and characterized their molecular functions in vitro and in vivo. Our results demonstrate that our newly identified microproteins are novel regulators of cell identity that play important roles in diverse functions such as induction of cellular differentiation, inhibition of EMT and mitochondrial metabolism, all of them under the umbrella of tumor suppression. Our group also hypothesized that the microproteins’ small size makes them ideal candidates to be shed by the cell and act as extracellular messengers. We have mined the pancreatic cancer-secreted microproteome for novel regulators of tumor progression and metastasis. Using proteogenomics in patient-derived samples, we have identified hundreds of microproteins secreted, soluble or coated in exosomes, by pancreatic tumors. The characterisation of our top candidates so far has shown that they can extrinsically promote tumor growth and metastasis. Altogether, our data advances our knowledge on the underexplored microproteome and provides pioneering evidence of its role in cancer cell plasticity and tumor communication.

This talk is part of the Genetics Seminar series.

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