Cell Signalling Laboratory
Head of laboratory
On this page:
Overview of research program
Normal growth and function of body tissues is dependent upon biochemical signals passing from one protein to another in tightly controlled pathways. If these signalling pathways become disrupted, perhaps because of changes in the hormones and growth factors which activate them, there can be a disruption in the balance of cell division and cell death which may lead to uncontrolled growth and cancer. The research carried out in the Cell Signalling Laboratory of the Hormones and Cancer Group is focussed on understanding how this transfer of information is regulated during normal cell growth, and investigating changes that occur in these pathways during the development of diseases such as cancer.
Our primary focus in this area lies in the role of a family of proteins called insulin-like growth factor binding proteins, or IGFBPs, in normal and malignant growth. There is good evidence that two of these proteins in particular, IGFBP-2 and IGFBP-3, may be involved in a variety of cancers, but the mechanisms underlying their regulation of cell growth and proliferation remain poorly understood. Using breast cancer cell culture models, we are investigating the signalling pathways used by these proteins to modulate tumorigenic properties such as proliferation, migration and invasion. Our recent studies have revealed a novel mechanism by which IGFBP-3 can enhance the growth effects of a variety of hormones known to be significant in breast cancer, and have implications for multiple processes critical for malignant growth and the spread of tumours. Our current research projects are aimed at delineating the signalling pathways modulated by IGFBP-2 and IGFBP-3 in normal and malignant cell growth, and identifying the functional effects of modulating the expression of these proteins.
Major funding sources
- Cancer Institute NSW
- Australian Research Council
Selected publications
Martin JL, Baxter RC (2007) Expression of insulin-like growth factor binding protein-2 by MCF-7 breast cancer cells is regulated through the PI3-kinase/Akt/mTOR pathway. Endocrinology 148:2532-2541
Martin JL, Jambazov S (2006) Insulin-like growth factor binding protein-3 in extracellular matrix stimulates adhesion of breast epithelial cells and activation of p44/42 MAPK. Endocrinology, 147: 4400-4409
Butt AJ, Martin JL, Dickson KA, McDougall F, Firth SM, Baxter RC (2004). Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: the role of altered epidermal growth factor signaling. J Clin Endocrinol Metab 89: 1950-1956.
Martin JL, Weenink SM, Baxter RC (2003) Insulin-like growth factor binding protein-3 potentiates EGF action in mammary epithelial cells: Involvement of p44/42 and p38 MAP kinases. J Biol Chem, 278: 2969-2976.
Salahifar H, Baxter RC, Martin JL (2000) Differential regulation of insulin-like growth factor binding protein-3 protease activity in MCF-7 breast cancer cells by estrogen and transforming growth factor-β 1. Endocrinology 141: 3104-3110.
Martin JL, Baxter RC (1999) Oncogenic ras causes resistance to the growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3) in breast cancer cells. J Biol Chem 274: 16407-16411.
Salahifar H, Baxter RC, Martin JL (1997) Insulin-like growth factor (IGF) binding protein-3 protease secreted by MCF-7 breast cancer cells: Inhibition by IGFs does not require IGF–IGFBP interaction. Endocrinology 138: 1683-1690.
Martin JL, Baxter RC (1991) Transforming growth factor-β stimulates production of insulin-like growth factor binding protein-3 by human skin fibroblasts. Endocrinology 128: 1425-1433.
Wood WI, Cachianes G, Henzel WJ, Winslow GA, Spencer SA, Hellmiss R, Martin JL, Baxter RC (1988) Cloning and expression of the growth hormone-dependent insulin-like growth factor-binding protein. Molec. Endocrinol. 2: 1176-1185
Baxter RC, Martin JL (1986) Radioimmunoassay of growth hormone-dependent insulin-like growth factor binding protein in human plasma. J. Clin. Invest. 78: 1504-1512
