Principal Investigator, Associate Professor of Histology and Embryology, School of Medicine, Department of Molecular Medicine, University of Padua, ITALY

Friday 27 August 2021 | 12:00 noon – ICGEB Trieste, ITALY

Mechano-metabolic control of chemotherapy resistance in dormant metastatic breast cancer cells

Hosts: S. Zacchigna

The tumor microenvironment (TME) is a key variable controlling cancer cell behavior. Important players in the TME are stromal and immune cells, but also the composition and physical properties of the extracellular matrix. So far, a soft TME has been considered tumor-suppressive, by keeping in check cell growth. Here we found that a soft TME can also play a pro-tumorigenic function, by promoting therapy resistance. Starting from an unbiased metabolomics approach, we found that the softness of the TME regulates cancer cell metabolism by empowering cystine uptake and glutathione synthesis. This depends on regulation of mitochondrial dynamics, leading to the activation of an antioxidant transcriptional response. In turn, this transcriptional and metabolic rewiring protects cancer cells from chemotherapy. This unveiled a liability to eradicate metastatic breast cancer cells dormant in the soft microenvironment of the lung tissue.