Characterisation Of A Novel Oncogene In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,118,325.00
Summary
Breast cancer affects 1 in 8 women in Australia. Cancer cells are able to spread to other sites in the body by a process known as metastasis which is the leading cause of breast cancer death. We have identified a gene which controls breast cancer metastasis and thereby may affect disease outcome. This grant aims to elucidate the mechanisms by which this gene regulates breast cancer metastasis.
Telomere Structural Abnormalities In Cells Using Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$522,122.00
Summary
The continuing growth of cancers depends on their cells being able to prevent shortening of chromosome ends (telomeres). Some cancers, including very aggressive brain and connective tissue tumours, achieve this via the Alternative Lengthening of Telomeres (ALT) process. We have evidence that the telomere structure of normal cells prevents ALT. Here we will examine how the telomere structure of ALT-positive cancer cells is changed, and whether reversing these changes inhibits ALT.
Cell survival and death are controlled by two processes known as apoptosis and autophagy. Apoptosis eliminates damaged cells whereas autophagy gets rid of faulty components in the cell. The Bcl-2 proteins regulate both processes. It is well established that dysfunctional Bcl-2 regulation leads to cancer. In this project, we aim to investigate if deregulated Bcl-2 control of autophagy also has a key role in cancer progression and to obtain a molecular picture of how this control is exerted.
The Role Of Somatic Mutations In CCCTC-binding Factor (CTCF) Binding Sites In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,114.00
Summary
The three dimensional organisation of genomic DNA has been recognised to play a crucial role in maintaining the stability and function of human cells. In cancer this organisation is often perturbed as a result of mutations to proteins that govern this process. This project will examine how mutations in the DNA may potentially alter the three dimensional organisation of cancer genomes and will identify links between these mutations with cancer development and patient prognosis.
The Contribution Of Host Caveolin-1 To Breast Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$517,992.00
Summary
Mortality in breast cancer rises to 80% in cases where secondary tumors form in other organs. To improve outcome, a better understanding of the processes involved in cancer spread is needed. Normal cells contribute to the growth and spread of a tumour and are a target for therapy. When a protein called caveolin-1 is lost from normal cells in a tumour, the prognosis for the patient is much worse. The aim of this project is to understand how this protein can regulate the spread of breast cancer.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
Alpha-actinin-4 As An Oncogenic Driver And Therapeutic Target In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$401,786.00
Summary
Despite the recent advances in targeted therapy and immunotherapy, curative treatment of metastatic melanoma remains an unmet health problem. In this project, we will potentially demonstrate that a protein called ACTN4 is abnormally expressed at high levels in melanoma cells and plays an important role for melanoma cell survival and resistance to treatment, and thus identify inhibition of ACTN4, either alone or in combination with other drugs, as a novel approach in the treatment of melanoma.
Role Of LncRNA IDH1-AS1 In Regulating C-Myc Driven-glycolysis And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$685,043.00
Summary
It is thought that understanding cancer metabolism will reveal vulnerabilities that can be exploited in the clinic. Indeed, compared to most normal cells, cancer cells utilise different fuels to sustain proliferation and to adapt to their environment. Herein we have discovered a molecular switch that regulates the key metabolic enzyme IDH1 and show this controls tumour growth. Given this switch may be active in 50% of cancers we anticipate our work will have significance to many cancer types.