Angela BACHI

Principal Investigator, Proteomics Lab, Head of Proteomics and Metabolomics Facility, IFOM ETS-The AIRC institute of Molecular Oncology, Milan, ITALY

BACE2 orchestrates tumor-microenvironment mechanical and metabolic interactions

Host: G. Del Sal

BACE2 is an aspartic protease upregulated in several solid tumors. High BACE2 expression correlates

with worse prognosis in melanoma, glioma, colon and pancreatic cancer. Physiologically it has been

involved in the maturation and secretion of amyloidogenic targets such APP in the brain and PMEL

in melanocytes. Recently, our lab established a link between the presence of PMEL amyloid fibrils

in the metastatic melanoma secretome and YAP activation, affecting cancer proliferation and drug

sensitivity. In particular, we demonstrated that Agrin is part of the extracellular amyloid plaques,

interacts with PMEL amyloid fibrils and is necessary to drive PMEL dependent YAP activation. We

further characterized the signaling cascade triggered by amyloids identifying its dependency of the

Hippo pathway core kinase LATS1. Further, we demonstrated that the presence of amyloid fibrils in

the extracellular space enhances the migration and invasion capacity not only of melanoma cells

but also in pancreatic ductal adenocarcinoma cells, suggesting a conserved mechanism adopted

by cancer cells to tame the tumor microenvironment.

We also observed that the BACE2 sheddase activity is responsible for the tuning of both intra and

extracellular lipid content highlighting a so far unknown way adopted by cancer cells to rewire lipid

metabolism to sustain their growth.

https://www.ifom.eu/en/cancer-research/programs/functional-proteomics.php
https://www.ifom.eu/en/cancer-research/research-labs/research-lab-bachi.php

Publications: https://pubmed.ncbi.nlm.nih.gov/?term=bachi+angela%5BAuthor%5D&sort=date

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