Imperial College London
Alternate

Professor Irene Miguel-Aliaga

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Genetics and Physiology
 
 
 
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Contact

 

+44 (0)20 3383 3907i.miguel-aliaga Website

 
 
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Location

 

232ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Martorell:2014:10.1371/journal.pone.0088413,
author = {Martorell, O and Merlos-Suarez, A and Campbell, K and Barriga, FM and Christov, CP and Miguel-Aliaga, I and Batlle, E and Casanova, J and Casali, A},
doi = {10.1371/journal.pone.0088413},
journal = {PLOS One},
title = {Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut},
url = {http://dx.doi.org/10.1371/journal.pone.0088413},
volume = {9},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functionsthat these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized.Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducingbenign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Rasmutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila’s intestinesshare many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activationof the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show thatcompound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-likeoutgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of celldifferentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markerspresent in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration inintestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeuticcompounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila,providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation andprogression.
AU  - Martorell,O
AU  - Merlos-Suarez,A
AU  - Campbell,K
AU  - Barriga,FM
AU  - Christov,CP
AU  - Miguel-Aliaga,I
AU  - Batlle,E
AU  - Casanova,J
AU  - Casali,A
DO  - 10.1371/journal.pone.0088413
PY  - 2014///
SN  - 1932-6203
TI  - Conserved Mechanisms of Tumorigenesis in the Drosophila Adult Midgut
T2  - PLOS One
UR  - http://dx.doi.org/10.1371/journal.pone.0088413
UR  - http://hdl.handle.net/10044/1/30016
VL  - 9
ER  -
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