skip to primary navigationskip to content
 

22.08.16 Simons lab reveal that imbalanced cell fate, rather than faster cell division, drives cancer development in oesophagus

last modified Aug 25, 2016 03:22 PM
Publishing in Nature Cell Biology with colleagues from the Sanger Institute, the Simons lab show that subtle changes in cell fate behaviour underlie tumour development
22.08.16 Simons lab reveal that imbalanced cell fate, rather than faster cell division, drives cancer development in oesophagus

Balance between dividing and non-dividing cells in normal epithelium vs tumour

A single dividing cell population with imbalanced fate drives oesophageal tumour growth

Julia Frede, Philip Greulich, Tibor Nagy, Benjamin D. Simons & Philip H. Jones, Nature Cell Biology (2016) DOI:10.1038/ncb3400  [Published online 22 August 2016]

Access a PDF of the paper here.

In this work combining genetic lineage tracing with biophysical modelling, Ben Simons' group examined the patterns of cell division in a mouse model of oesophageal cancer.  They found a surprising result: tumour growth was not driven by faster cell division in a subset of 'cancer stem cells', but by a subtle increase in production of dividing cells over non-dividing cells.  If the same mechanisms are shown to underlie tumour development in humans, this insight offers a potential new strategy for blocking tumour growth by targeting imbalanced cell fate.

 

Abstract from paper:

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.

 

Abstract reprinted by permission from Macmillan Publishers Ltd: Nature Cell Biology, advance online publication, 22 August 2016 (DOI:10.1038/ncb3400)

Figure adapted by permission from Macmillan Publishers Ltd: Nature Cell Biology, (DOI:10.1038/ncb3400), copyright 2016.

 

See also this news article from Cancer Research UK.

 

Read more about research in the Simons lab.

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

combinedLogo x3 trans2018

 

Share this

A walk through tau therapeutic strategies

Labeling strategies matter for super-resolution microscopy: a comparison between HaloTags and SNAP-tags

Stem Cell-Derived Human Gametes: The Public Engagement Imperative

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment

Comparative Epigenomics Reveals that RNA Polymerase II Pausing and Chromatin Domain Organization Control Nematode piRNA Biogenesis

Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis

Constrained actin dynamics emerges from variable compositions of actin regulatory protein complexes

Microtubules Deform the Nuclear Membrane and Disrupt Nucleocytoplasmic Transport in Tau-Mediated Frontotemporal Dementia

Drosophila IMP regulates Kuzbanian to control the timing of Notch signalling in the follicle cells

Challenges in unsupervised clustering of single-cell RNA-seq data

Engineering vasculature: Architectural effects on microcapillary-like structure self-assembly

ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks

Altered γ-Secretase Processing of APP Disrupts Lysosome and Autophagosome Function in Monogenic Alzheimer’s Disease

Helicase subunit Cdc45 targets the checkpoint kinase Rad53 to both replication initiation and elongation complexes after fork stalling

Competition for Mitogens Regulates Spermatogenic Stem Cell Homeostasis in an Open Niche

Link to full list on PubMed