REGULATION OF MICROTUBULE DYNAMICS BY LIM KINASE1 (LIMK1)
Funder
National Health and Medical Research Council
Funding Amount
$386,020.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. We have found that LIMK1 is very important in controlling the polymerisation of one of the most ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. We have found that LIMK1 is very important in controlling the polymerisation of one of the most abundant molecules in the cell, actin. We have now preliminary data to show that LIMK1 also controls another important cellular protein, tubulin. Changes in tubulin polymerisation are of extreme importance for cell division and drugs affecting the state of tubulin are very potent as anti-cancer drugs. The goals of this research are: (1) To confirm that LIMK1 regulates the polymerisation of tubulin and (2) To demonstrate that LIMK1 regulates tubulin polymerisation by controlling the activity of p25, a protein involved in tubulin polymerisation that is modified by LIMK1. The results from this research will be highly significant because LIMK1 is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise. Therefore, we have to identify the other functions of LIMK1 to eliminate the possibility that drugs that inhibit LIMK1 and metastasis don't affect other organs and cells in the body. New molecules regulated by LIMK1 may also be suitable targets for drug development because through their inhibition we may also regulate other LIMK1 activities and possibly metastasis.Read moreRead less
Deregulation Of Ribosome Signalling, Synthesis And Function During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
Summary
A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy suggesting that it may play a causal role in cancer formation. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective in inhibiting the growth of some tumours. This study will examine the mechanisms of deregulation of ribosome biogenesis and function duri ....A major feature of tumour progression is accelerated cell growth and protein synthesis. Moreover, increased synthesis of ribosomes (the protein synthetic machinery) is associated with malignancy suggesting that it may play a causal role in cancer formation. In support of this, specific inhibitors of both ribosome biogenesis and function are extremely effective in inhibiting the growth of some tumours. This study will examine the mechanisms of deregulation of ribosome biogenesis and function during cancer formation and assess for the first time whether aberrant regulation of ribosome biogenesis and function directly contributes to the initiation and-or progression of cancer.Read moreRead less