Paracrine signalling in breast cancer - role of kinases in growth promotion
Project fact file
Dr Anna Grabowska
School / Division
Division of Cancer and Stem Cells
Technically-intensive/specialised research projects with high consumable costs
There is growing recognition of the importance of the tumour microenvironment (especially cells within the stroma, including mesenchymal cells) in determining biological characteristics of cancer cells including progression and drug resistance1-3. Breast cancer is known to have a marked stromal component, and thus, paracrine signalling between mesenchymal and cancer epithelial cells is thought to be important in promoting tumour progression. There are currently limited treated options available, in particular, for the triple negative subtype which lacks a number of the cell surface molecules against which currently available therapies are directed.
Using a co-culture system, in which we have shown that mesenchymal stem cells (MSCs) promote the growth of breast cancer epithelial cells, we have recently carried out a screen using an siRNA library targeting human kinases to identify molecules involved in the signalling cascades that promote this growth. Such molecules provide potential novel druggable targets for development of new therapeutic agents. The aim of this project is to further characterise these kinases and their involvement in growth and drug sensitivity using 2D and 3D co-culture models of breast cancer using RNAi and small molecule inhibitors.
1) Martin FT, et al.. Breast Cancer Res Treat, 2010317-26
2) Casey T, et al., 2009. 114:47-62
3) Shimoda M, et al.. Seminars in Cell & Developmental Biology, 2010. 21:19-25