Cell Cycle and Cancer - PhD and honours Projects - Regulation of proliferation and metastasis in breast cancer
Regulation of proliferation and metastasis in breast cancer
Project Type
PhD
Summary
A critical substrate of CDKs is the retinoblastoma tumour suppressor gene product, pRb, which inhibits G1-S phase cell cycle progression by inhibiting the activity of E2F transcription factors. pRb inhibits E2F through recruitment of histone deacetylases (HDACs) via a retinoblastoma binding protein (RBP1). Studies in our laboratory show that RBP1 is phosphorylated by CDKs leading to its dissociation from pRb, to affect its tumour suppressor function. In addition to binding to pRb, RBP1 binds to the breast cancer metastasis suppressor, Brms1, which is a transcriptional regulator. Brms1 function is important for suppressing the spread of breast cancer cells from the original tumour site to distant organs. Our work suggests that CDK-mediated phosphorylation of RBP1 and Brms1 affects the metastasis suppressor function of Brms1. Further studies will involve understanding how CDK-mediated phosphorylation of RBP1 and Brms1 affects metastasis suppressor function. These studies for the first time suggest that deregulated CDK activity can lead to increased proliferation and metastasis in breast cancer. Understanding the mechanisms of increased proliferation and metastasis of breast cancer cells is important for developing new therapeutic approaches to treat this disease.
Supervisor: Dr Boris Sarcevic