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Understanding tissue context influences on intratumour heterogeneity
Franziska Michor1, Valerie M Weaver2
1Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, and Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02215, USA.
Nature Cell Biology
|April 3, 2014
Summary
The tumor microenvironment influences cancer cell diversity. A dynamic signaling pathway involving TGFBR3 and JUND, dependent on the extracellular matrix, alters cell properties and potentially malignancy risk.
Area of Science:
- Cell biology
- Cancer research
- Extracellular matrix dynamics
Background:
- Intratumour heterogeneity is a hallmark of human cancers.
- The role of the tumour microenvironment in driving this heterogeneity remains poorly understood.
Purpose of the Study:
- To investigate the influence of the tumour environment on cellular heterogeneity in mammary epithelial cells.
- To identify specific signalling pathways and extracellular matrix interactions involved in cell state transitions.
Main Methods:
- Utilized single basal-like mammary epithelial cells.
- Analyzed gene expression states and their transitions.
- Investigated extracellular matrix-dependent signalling.
Main Results:
- Identified a dynamic TGFBR3-JUND signalling circuit.
- Demonstrated that this circuit is modulated by the extracellular matrix.
- Observed that cell transitions between gene expression states alter cell properties.
Conclusions:
- The tumour environment, through extracellular matrix interactions, can dynamically regulate signalling pathways like TGFBR3-JUND in mammary epithelial cells.
- These dynamic changes in cell states may influence a cell's propensity towards malignancy, contributing to intratumour heterogeneity.
