Investigating the Role of the IGF-1R in Breast Cancer Stem Cells

Overview

Topic status: We're looking for students to study this topic.

The Insulin-like growth factor (IGF) family is a highly relevant growth regulatory system in both normal mammary gland development and breast cancer. The majority of the functional effects modulated via the IGF family ligands, IGF-I and IGF-II, are a result of their binding and activation of the cell surface type-1 IGF receptor (IGF-1R). The activation of the IGF-1R and downstream pathways has critical roles in the normal development of many tissues and is believed to be important for the maintenance of tissue resident adult stem cells. Furthermore, signalling mediated via the IGF-1R is required for Embryonic Stem cell self-renewal, therefore, suggesting an import role for the IGF-1R in stem cell biology. Taken together with the well established role of the IGF-1R in breast tumour growth and metastasis, this project aims to determine whether the IGF-1R has a functional role in breast cancer stem cells (BrCSCs). Using both shRNA mediated suppression of IGF-1R expression and pharmacologic inhibition of IGF-1R signalling using small molecule inhibitors, the project will interrogate the effect of IGF-1R suppression on BrCSC frequency and tumourigenic properties in cell lines that contain high numbers of BrCSCs (eg SUM159, MDA-MB-231). Furthermore, the project will determine if the IGF-1R can be used as a cell surface marker for identifying populations of BrCSCs.

Hypothesis: The inhibition of IGF-1R signalling will decrease the self-renewal capacity of BrCSCs and reduce the inherent tumourigenic properties of these cells.

Aim 1: Determine the cell surface expression and activation status of the IGF-1R in BrCSCs isolated from breast cancer cell lines

Aim 2: Determine if the cell surface expression of the IGF-1R in combination with
putative BrCSC markers (eg CD44/CD24, ALDH) can be used to isolate highly enriched
populations of BrCSCs

Aim 3: Validate the functional role of IGF-1R signalling in BrCSCs using both shRNA and pharmacologic inhibition strategies

Methods and techniques that will be developed in the course of this project:

  • Cell culture of breast cancer cell lines
  • FACS analysis and isolation of BrCSC populations
  • Western blotting, qRT-PCR and Immunohistochemistry
  • Lenti-viral mediated shRNA gene knockdown
  • In vitro functional assays for BrCSC properties
Study level
Honours
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Contact
Please contact the supervisor.