The extracellular matrix supports breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism.

ABSTRACT: Breast tumours are embedded in a collagen I-rich extracellular matrix (ECM) network, where nutrients are scarce due to limited blood flow and elevated tumour growth. Metabolic adaptation is required for cancer cells to endure these conditions. Here, we demonstrated that the presence of ECM supported the growth of invasive breast cancer cells, but not non-transformed mammary epithelial cells, under amino acid starvation, through a mechanism that required macropinocytosis-dependent ECM uptake. Importantly, we showed that this behaviour was acquired during carcinoma progression. ECM internalisation, followed by lysosomal degradation, contributed to the up-regulation of the intracellular levels of several amino acids, most notably tyrosine and phenylalanine. This resulted in elevated tyrosine

SUBMITTER: Nazemi M 

PROVIDER: S-EPMC10791009 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature