Affiliations: 1) Medical Research Council (MRC) London Institute of Medical Sciences, London; 2) Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London
Keywords: h. tumorigenesis; i. metastasis
Epidemiological studies have shown that obesity promotes the development and progression of various cancers, including colorectal cancers. However, while cancer is a genetically heterogeneous disease, little is known about the genetic characteristics of tumours that associate with obesity. Here, we combine a series of Drosophila models of colorectal cancer with a Drosophila model of diet-induced obesity to explore whether and how tumours of different genetic profiles exhibit different invasiveness in response to obesity.
Using the dissemination of tumour cells into the abdominal cavity as a quantitative readout to assess tumour invasiveness, we demonstrate that obesity modulates the invasiveness of different tumours to different degrees. Furthermore, we found that tumours of different genetic profiles respond to obesity with different directionality; some tumours exhibited increased invasiveness in response to obesity, while other tumours were resistant to the effects of obesity.
RNA-Sequencing and comparative analysis of different tumours revealed Reactive Oxygen Species (ROS) as an important mediator that modulates the invasiveness of tumours in response to obesity. We demonstrate that dietary and genetic manipulation of ROS levels has a functional effect on the invasiveness of tumours.
Our observations indicate that the genetic profiles of tumours have a significant impact on the tumour’s response to obesity. This highlights the importance of stratification of tumours in understanding the relationship between obesity and cancer. Our work also demonstrates the usefulness of Drosophila as a model system to study the connection between obesity, tumour heterogeneity, and tumour invasiveness.