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Epigenetic regulation of EMT in 3D patient-relevant lung cancer models

Project fact file

Supervisor(s)
Drs Anna Grawbowska, Cinzia Allegrucci and David Onion
School / Division
Schools of Medicine, Veterinary Medicine and Science, Life Sciences 
Keywords
epigenetics Pre-clinical modelling tumour microenvironment invasion.metastasis paracrine signalling
Fee band
Technically-intensive/specialised research projects with high consumable costs
Date posted
July 2017

Project description

There is growing awareness of the importance of the tumour microenvironment (TME) in affecting tumour
progression and drug response1, with important roles for stromal cells including fibroblasts and interactions with
extracellular matrix (ECM).

The TME is known to influence epithelial-mesenchymal transition (EMT)2, a normal developmental process which,
in cancer, is involved in invasion and metastasis. In addition, it is associated with the cancer stem cell
phenotype which is in turn related to drug resistance and tumour recurrence following treatment.3

EMT is regulated by a complex transcriptional network4 with a number of signalling pathways involved, including
Wnt, integrin signalling, TGF-β, and Notch. These in turn are affected by epigenetic alterations in lung cancer.5

Epigenetic de-regulation has been recently shown to be a key driver of NSCLC and correlates with poor prognosis.6

We have established models of lung cancer including early passage patient-derived lines and established cell lines (of
different mutational and histological subtypes) which have been characterised for EMT status and which can be grown
in 3D models incorporating ECM components and stromal cells. This provides a unique opportunity to investigate
epigenetic regulation of EMT and its downstream effects in terms of invasion, metastasis and drug resistance under
conditions that closely resemble the in vivo TME.

  1. Box C. et al. Semin Cancer Biology, 2010
  2.  Tsuji T. et al. Cancer Res, 2009;
  3. Scheel C., Weinberg R.A. Semin Cancer Biol, 2012;
  4. Venkov, C., et al. PLoS ONE, 201
  5. Mazieres J. et al. Cancer Res, 2004
  6. Lv T. et al. PLoS One 2012

 

 

 

School of Medicine

University of Nottingham
Medical School
Nottingham, NG7 2UH

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