A single dividing cell population with imbalanced fate drives oesophageal tumour growth
A single dividing cell population with imbalanced fate drives oesophageal tumour growth
Understanding the cellular mechanisms of tumour growth is key for designing rational anticancer treatment. Here we used genetic lineage tracing to quantify cell behaviour during neoplastic transformation in a model of oesophageal carcinogenesis. We found that cell behaviour was convergent across premalignant tumours, which contained a single proliferating cell population. The rate of cell division was not significantly different in the lesions and the surrounding epithelium. However, dividing tumour cells had a uniform, small bias in cell fate so that, on average, slightly more dividing than non-dividing daughter cells were generated at each round of cell division. In invasive cancers induced by KrasG12D expression, dividing cell fate became more strongly biased towards producing dividing over non-dividing cells in a subset of clones. These observations argue that agents that restore the balance of cell fate may prove effective in checking tumour growth, whereas those targeting cycling cells may show little selectivity.
967-978
Frede, Julia
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Greulich, Philip
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Nagy, Tibor
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Simons, Benjamin D.
02e0ea52-9b7f-4b80-a856-a22cc1991ba3
Jones, Philip H.
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September 2016
Frede, Julia
45a1abf2-49bc-4301-9bf2-39798fdb8dc1
Greulich, Philip
65da32ad-a73a-435a-86e0-e171437430a9
Nagy, Tibor
2823172b-7b02-4b66-8d98-dbcf486877f2
Simons, Benjamin D.
02e0ea52-9b7f-4b80-a856-a22cc1991ba3
Jones, Philip H.
f263e68c-4612-4e26-884c-0ff65f824611
Frede, Julia, Greulich, Philip, Nagy, Tibor, Simons, Benjamin D. and Jones, Philip H.
(2016)
A single dividing cell population with imbalanced fate drives oesophageal tumour growth.
Nature Cell Biology, 18 (9), .
(doi:10.1038/ncb3400).
Abstract
Understanding the cellular mechanisms of tumour growth is key for designing rational anticancer treatment. Here we used genetic lineage tracing to quantify cell behaviour during neoplastic transformation in a model of oesophageal carcinogenesis. We found that cell behaviour was convergent across premalignant tumours, which contained a single proliferating cell population. The rate of cell division was not significantly different in the lesions and the surrounding epithelium. However, dividing tumour cells had a uniform, small bias in cell fate so that, on average, slightly more dividing than non-dividing daughter cells were generated at each round of cell division. In invasive cancers induced by KrasG12D expression, dividing cell fate became more strongly biased towards producing dividing over non-dividing cells in a subset of clones. These observations argue that agents that restore the balance of cell fate may prove effective in checking tumour growth, whereas those targeting cycling cells may show little selectivity.
Text
Frede et al 2016 accepted version
- Accepted Manuscript
More information
Accepted/In Press date: 19 July 2016
e-pub ahead of print date: 22 August 2016
Published date: September 2016
Organisations:
Applied Mathematics
Identifiers
Local EPrints ID: 410448
URI: http://eprints.soton.ac.uk/id/eprint/410448
ISSN: 1465-7392
PURE UUID: 5c57ffea-f2e4-4b7c-8e3f-59be0b14d3e0
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Date deposited: 08 Jun 2017 16:31
Last modified: 16 Mar 2024 04:17
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Contributors
Author:
Julia Frede
Author:
Tibor Nagy
Author:
Benjamin D. Simons
Author:
Philip H. Jones
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