Cancer invasion and metastasis
Lab head: Dr Guy Lyons
Location: Dermatology Research Labs, Rm W350 Blackburn Bldg
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, 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 oncogenic papilloma viruses and processes such as epithelial-mesenchymal transitions in tumour progression and resistance to therapy are also being studied, using innovative cell and animal models. Translation of these findings to improving treatments, particularly radiation therapy, is being undertaken.
Lab members: Dr Nicole Bryce, Ms Naomi Delic, Ms Ronak Hojatpanah, Dr Cathy Payne, Dr Vani Raviraj, Mr Paul Sou
Funding: NHMRC, Human Frontiers Science Program
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, whole animal bioimaging, biochemical and immunological characterisation of proteins, and flow cytometry.
Publications: Key publications related to this project are:
- 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
- Raviraj V, Fok S, Zhao J, Chien HY, Lyons JG, Thompson EW and Soon L (2012) "Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices." BMC Cell. Biol. 13, 12
- Lyons JG, Patel V, Roue N, Fok SY, Soon L, Halliday GM and Gutkind JS (2008) "Snail up-regulates proinflammatory mediators and inhibits differentiation in oral keratinocytes." Cancer Res. 68, 4525-4530
- Sou PW, Delic NC, Halliday GM and Lyons JG (2010) "Snail transcription factors in keratinocytes: Enough to make your skin crawl." Int. J. Biochem. Cell Biol. 42, 1940-1944
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 test the clonal cooperation hypothesis in an established in vivo experimental model of human squamous cell carcinoma (SCC). Candidate oncogenes will be introduced independently into non-tumorigenic SCC cells, using plasmid and viral vectors. Emphasis will be placed on oncogenes that increase the motility or proliferation of cells. Lines expressing individual oncogenes will be tested for their ability to display several malignant behaviours, both on their own and when mixed with other oncogene-expressing lines, to determine whether clonal cooperation occurs. Cell culture experiments aimed at determining whether clonal cooperation contributes to proliferation and invasion of the extracellular matrix will be undertaken, and in vivo tumour formation will also be tested.
The methods encountered to undertake this project will include recombinant DNA technology, mammalian cell culture, live-cell microscopy, 3-dimensional fluorescent microscopy, intravital microscopy and bioimaging of living mice.
Co-supervisors: Vani Raviraj, Nicole Bryce, Gary Halliday
Keywords: Cancer, Genetic processes, Evolutionary Theory