Our group identified and functionally characterised a novel coiled-coil protein that locates to the centrosome and cytoplasm, which we have named Cep55 (Dev Cell 2005 9(4):477-88). Centrosomes play a critical role in processes that ensure proper segregation of chromosomes and maintain the genetic stability of human cells. They contribute to mitotic spindle organization and regulate cytokinesis and cell cycle progression. Characterisation of Cep55-depleted cells revealed that it is indispensable for cytokinesis. Our laboratory performed database mining of microarray expression profiles to ascertain expression of Cep55 in cancer. As expected, the EST corresponding to Cep55, designated FLJ10540, was elevated in a wide range of human cancers including gastric, hepatocellular, colon, lung, pancreatic, and breast. Consistent with this, increased centrosome number and abnormal centrosome morphology have been described in many human tumours. It is therefore likely that a correlation exists between aberrant genetic instability with Cep55 overexpression, which may lead to cancer progression and metastasis. In line with this, Cep55 was amongst 19-gene signature identified associated with poor prognosis of breast cancer. Moreover, it is known that p53 negatively regulates Cep55 stability and loss of p53 enhances Cep55 expression in cancer. The overall aim of this project is to decipher the mechanism by which Cep55 regulates breast cancer progression and metastasis. This project aims to study the functional interplay between Cep55overexpression and p53 loss in regulating breast cancer progression and metastasis and to assess the functional role of Cep55 in regulating tumour angiogenesis and microenvironment during disease progression and metastasis.
Expected outcomes and deliverables
Scholars will gain skills in cell biology, molecular biology and/or animal techniques including tissue culture, immunofluorescence, western blotting, FACS, animal handling and dissections and Xenograft Tumour Models.
- Suitable for students with a background in biology who are looking to undertake Honours or a PhD in the future.