ArticlePLoS biology2024
The extracellular matrix supports breast cancer cell growth under amino acid starvation by promoting tyrosine catabolism.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- A noncanonical function of the tyrosine degradation enzyme FAH drives CDK4/6 inhibitor resistance in breast cancer.Science advances · 2026Article
- Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation.PLoS biology · 2026Article
- Glycolytic suppression of cell adhesion promotes thyroid morphogenesis in response to nutrition.EMBO reports · 2026Article
- Beyond the scaffold: extracellular matrix uptake in breast cancer.Biochemical Society transactions · 2026Review
- Decoding the Collagenome in Breast Cancer: Mechanotransduction, Microenvironment, and Translational Opportunities.International journal of molecular sciences · 2026Review
- Circulating Thioredoxin 1 as an Adjunct to Mammography for Breast Cancer Detection: A Multicenter Clinical Validation Study.Cancers · 2026Article
- Serum SOS1 as a prognostic biomarker and therapeutic target for progressive liver disease.iScience · 2026Article
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Integrative Multi-Omics Reveals Microbiome and Genome Streamlining Underlie Ecological Divergence in Chinese and XinjiangInternational journal of molecular sciences · 2026Article
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Development of a lactate metabolism signature for predicting homologous recombination repair status in breast cancer.Scientific reports · 2026Article
- Metabolic rewiring of the tumor microenvironment: therapeutic intervention of multi-pathway adaptations to impede cancer metastasis.Frontiers in molecular biosciences · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Article
- Distinct Immune Landscape and Gene Expression Profiles in Breast Cancer: Young versus Non-Young Patients.Breast care (Basel, Switzerland) · 2025Article
- Differential cell survival outcomes in response to diverse amino acid stress.Life science alliance · 2025Article
- Understanding and measuring mechanical signals in the tumor stroma.FEBS open bio · 2025Review
- Deciphering key chemotherapeutic drug targets within tyrosine metabolism for breast cancer and advancing a wide-ranging diagnostic strategy.Discover oncology · 2025Article
- The Rab25-ADAMTS5 axis as a previously undescribed mechanism for sensing tumor microenvironment complexity.The FEBS journal · 2025Article
- The role of collagen type VI alpha 6 chain as a potential tumor suppressor in breast cancer: an immune regulation perspective.BMC cancer · 2025Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
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 catabolism on ECM under starvation, leading to increased fumarate levels, potentially feeding into the tricarboxylic acid (TCA) cycle. Interestingly, this pathway was required for ECM-dependent cell growth and invasive cell migration under amino acid starvation, as the knockdown of p-hydroxyphenylpyruvate hydroxylase-like protein (HPDL), the third enzyme of the pathway, opposed cell growth and motility on ECM in both 2D and 3D systems, without affecting cell proliferation on plastic. Finally, high HPDL expression correlated with poor prognosis in breast cancer patients. Collectively, our results highlight that the ECM in the tumour microenvironment (TME) represents an alternative source of nutrients to support cancer cell growth by regulating phenylalanine and tyrosine metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.