Cancer invasion and metastasis

Lab head: Assoc. Prof. Guy Lyons
Location: Centenary Institute

The key characteristic that defines a tumour as being malignant is its ability to spread locally (invade) and to distant sites (metastasise). Our group is studying the molecular, genetic and cellular mechanisms of how cancers progress from a normal tissue to a malignant tumour. Our focus is on squamous cell carcinomas of the skin, eye, mouth and throat. We are particularly interested in tumour ecology, and are exploring the interactions of cancer cells with their tumour microenvironment and the mechanisms driving the evolution of clones of cells in cancer. The roles of cancer-related genes in driving proliferation and motility of cells are studied, using innovative cell, animal and computer models. The knowledge gained from this project will enable the improvement of the prevention and treatment of cancer.

Lab members: Dr Rumana Khanom, Ms Naomi Delic, Dr Vani Raviraj
Funding: Worldwide Cancer Research Fund
Research approach equipment: This program encompasses a range of molecular and cell biological methods, including: cell culture models, live-cell imaging, plasmid and virus vector construction, quantitative gene expression analysis, small animal models, intravital microscopy, and computer simulation models.

Key publications related to this project are:

  • Lobo EP, Delic NC, Richardson A, Raviraj V, Halliday GM, Di Girolamo N, Myerscough MR, and Lyons JG (2016) "Self-organized centripetal movement of corneal epithelium in the absence of external cues." Nat Commun 7:12388.
  • Lyons JG, Lobo E, Martorana AM and Myerscough MR (2008) "Clonal diversity in carcinomas: its implications for tumour progression and the contribution made to it by epithelial-mesenchymal transitions." Clin. Exp. Metastasis 25: 665-677

Genes and cell-cell interactions in tumour progression

Primary supervisor: Guy Lyons

Cancer is a disease in which cells acquire mutations in key genes that change their behaviour. Under pressures of limiting space and nutrients, cells that have an advantage in survival and proliferation are selected and dominate the tissue. This mutation and selection process is, in fact, an example of evolution. The clonal cooperation hypothesis of tumour progression predicts that genetically distinct clones of tumour cells interact in order for the tumour as a whole to progess to malignancy. These interactions allow the tumour cells to invade tissues locally and spread to draining lymph nodes and other organs.

This project will investigate the role of cooperative interactions between clones of cells in driving tumour progression. It uses live cell microscopy of genetically modified cells to identify what types of genes can interact to affect proliferation and motility in different individual cells. Computer simulations are used to predict the effects of these cell-cell interactions on the population of cells as a whole, and how they affect the clonal evolution of the cells. 

The methods encountered to undertake this project will include some of the following techniques: recombinant DNA technology, mammalian cell culture, live-cell microscopy, and computational biology. 

Discipline: Pathology
Keywords: Cancer, Evolution, Computational biology