Genes and cell-cell interactions in cancer progression.

Summary

Oncogenes, tumour suppressor genes and cell-cell interactions in cancer: which are important in driving tumour progression and invasion in squamous cell carcinomas?

Supervisor(s)

Dr Guy Lyons

Research Location

Central Clinical School, Dermatology Research Labs

Program Type

Masters/PHD

Synopsis

Cancer is a genetic disease.  Cancer causing genes are mutated by radiation, viruses and mutagenic chemicals. Despite the identification of many of these genes, others remain to be identified, and fundamental questions of how they function, particularly in interaction with oneanother, remain to be answered. This project aims to determine the cellular and molecular mechanisms by which candidate oncogenes and tumour suppressor genes contribute to the formation of squamous cell carcinomas (SCCs) of the skin and of the head and neck region, two of the most common sites for cancer. Of particular interest are genes involved in the progression from benign tumours, which are non-invasive and usually easily treated, to malignant tumours, which spread invasively from the site of origin and are difficult to treat successfully. Candidate oncogenes and tumour suppressor gene knockdown sequences are introduced into non-tumorigenic SCC precursor cells, using viral vectors, and then tested in combinations for the ability to participate in various cell and molecular biological processes that are important to tumour progression. These include cell culture experiments aimed at determining whether they contribute to invasion of the extracellular matrix, evasion of terminal differentiation, proliferation and radiation resistance. This project is a collaboration with Prof. Gary Halliday and is currently funded by grants from the NHMRC and Cancer Council NSW.

Additional Information

Techniques: This project encompasses a range of molecular and cell biological methods and analyses, including cell culture, plasmid and virus vector construction, gene expression analysis, some small animal handling and microscopy.  Both in vivo and in vitro models for squamous cell carcinogenesis are established in the laboratory. Potential research areas for PhDs:

1. Cell-cell interactions in squamous cell carcinogenesis.  This project investigates the role of interclonal cooperativity in tumour progression by examining the ability of oncogenes and tumour suppressor genes to promote growth, radiation resistance, invasion and metastasis, when they are present in different cells within a cancer.
2. Chromatin remodelling proteins as tumour suppressors.  Components of the SWI/SNF complex are down-regulated during tumour progression, and we are using knock-out animals and cell lines to establish their functional significance in skin cancer formation.
3. Role of Snail in squamous cell carcinogenesis.  “Snail” is a transcription factor and putative oncogene that down-regulates epithelial-specific gene expression and promotes invasion of carcinoma cells into the extracellular matrix, and we are elucidating the mechanisms by which this occurs in squamous cell carcinomas of the skin and the mouth and throat. 

Keywords

Skin Cancer, Oncogene, Signal transduction, Transcription, Cancer & leukaemia, Cell biology, Genes in biology & medicine, head and neck cancer, tumour progression, invasion, metastasis, extracellular matrix, photobiology, tissue engineering

Opportunity ID

The opportunity ID for this research opportunity is: 102