Collagen I promotes cancer cell survival via amino acid import and mTORC1/S6 activation
What this study shows
Collagen I drives alpha2beta1 integrin-dependent mTORC1/S6 activation and membrane localization of the LAT1-4F2hc amino acid transporter, sustaining essential amino acid supply and cancer cell survival in nutrient-poor, collagen-rich tumor stroma; LAT1-4F2hc is upregulated in basal-like breast/pancreatic tumors and correlates with poor prognosis.
Abstract
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Invasive breast and pancreatic cancer cells thrive within a collagen I-rich, poorly perfused extracellular matrix (ECM) network, necessitating robust metabolic adaptation to endure nutrient deficiency, such as glucose starvation. Here we demonstrate that collagen I is critical for the survival and growth of breast and pancreatic cancer cells. Mechanistically, collagen I promotes alpha2 beta1 integrin-dependent S6 phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) and drives the membrane localisation of the (LAT1)-4F2hc amino acid transporter.
Read the full abstract on PubMed →At a glance
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| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human breast and pancreatic cancer cell lines (2D/3D culture)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Human breast and pancreatic cancer cell lines (2D/3D culture) |
| Journal | PLOS Biology |
| Year | 2026 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1371/journal.pbio.3003555 · PMID 42758789 |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
People in the Atlas
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Cell biologist in Elena Rainero's lab at the University of Sheffield who studies how the collagen-rich matrix around tumours feeds cancer cells when nutrients run short
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Studies how cancer cells use the extracellular matrix as a nutrient and signaling source; senior author on a 2026 study linking collagen I to mTORC1 activation in cancer cells
More: 4 other authors
No profile yet: Yanes B, Vancauwenberghe E, Oyelade I, Walker H
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | collagen I matrix exposure; alpha2beta1 integrin inhibition; LAT1-4F2hc inhibition; glucose starvation |
| Target | mTORC1 / S6 phosphorylation and the LAT1-4F2hc amino acid transporter |
| Model | human breast and pancreatic cancer cell lines in 2D and 3D culture |
| Effect | Collagen I raised integrin-dependent mTORC1 activity and membrane LAT1-4F2hc, sustaining amino acid supply and cancer cell survival, and blocking either step reduced growth and invasion. |
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