Regulation Of Mitogenic Signalling Via The Gab2 Docking Protein
Funder
National Health and Medical Research Council
Funding Amount
$141,750.00
Summary
Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. F ....Cell proliferation is regulated by growth factors which bind to specific receptors on the cell surface. These receptors then transmit a signal to the interior of the cell instructing it to divide. Inside the cell, the signal is transmitted by signalling proteins. Importantly, aberrant signalling by growth factor receptors or intracellular signalling molecules can contribute to cancer. We have recently demonstrated that the signalling protein Gab2 is overexpressed in a subset of breast cancers. Furthermore, we have identified that another protein, termed PKB, can 'switch off' signalling by Gab2, and that deregulated signalling by Gab2 can make cells cancerous. The aim of this project is to characterize how PKB regulates Gab2, and to investigate whether this mechanism is impaired in human cancers, leading to enhanced Gab2 signalling. The research will provide important information regarding how growth factor signals are transmitted inside cells, and may identify a new cancer-causing gene.Read moreRead less
Colorectal Cancer - Molecular Basis To Targeted Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$19,818,386.00
Summary
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Acute myeloid leukaemia (AML) is a major health problem with only about one third of patients being cured. In addition therapies have changed little over the last 20 years. However there is optimism that with greater knowledge of the biochemical changes in AML that are caused by genetic mutations, more effective treatments will be developed. This project therefore aims to increase understanding of the biochemical interplay between two proteins called c-Cbl and Flt3 that are altered in AML.
Role Of A Novel Tks5-Nck Signaling Pathway In Cancer Invasion
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
Invasion and metastasis are major causes of death in cancer patients. Our research has uncovered a pathway that increases the invasive potential of tumour cells in vitro. We now aim to determine if the pathway is relevant in invasion and metastasis in clinically relevant models; how a drug targeting the pathway affects invasion and; the extent to which the pathway is active in human tumours. These studies may identify a new molecular target for anti-invasive drugs.
In Vivo Role Of LMO4 And Isolation Of An LMO4-containing Proteosome In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understandi ....Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes thought to contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. Nuclear regulatory proteins have been implicated in many different types of cancers and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their structural properties and biological roles, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific regulatory molecule which we recently demonstrated to be overexpressed in 56% of human primary breast cancers and in 38% of pre-invasive ductal carcinoma in situ. These studies will include defining its normal biologic function and identification of the proteins that this regulator associates with in breast cancer cells.Read moreRead less
This project seeks to evaluate the role of new cell growth regulating pathway in the development of moles and melanoma. In particular, we will determine at which stage during tumour progression disruption of this pathway occurs, and whether its loss is associated with melanoma patient survival. Identification of the cancer-related changes that occur when this pathway is aberrant may ultimately lead to the development of novel therapies to treat melanoma.