Centre for Cancer Research Student Projects

Cell Adhesion Signalling Research Projects

Regulation of cell migration by integrin linked kinase
Project leader: Assoc Prof Greg Hannigan
Phone: 9594 7245

Although cancer involves dysregulation of normal process such as proliferation and apoptosis, metastatic cancer cell migration is a highly regulated event involving interactions between cellular signaling proteins and the actin cytoskeleton. Massive cytoskeletal reorganizations drive changes in cell shape and polarity in response to external migratory cues. Integrin linked kinase (ILK) is an essential molecule that physically links integrin receptors in the plasma membrane to the actin cytoskeleton, and transduces signals regulating cytoskeletal reorganization and cell migration. Rhabdomyosarcoma (RMS) are metastatic tumors that derive from skeletal muscle precursor cells. We have discovered that ILK is required for RMS cell migration toward factors elaborated within the tumor microenvironment, such as VEGF. We find that ILK regulates RMS migration in cooperation with another important signaling protein kinase, mTOR. This project will study the interaction between ILK and mTOR in normal skeletal myoblasts and RMS cells.

The work involves proteomic (mass spectrometry) and biochemical analyses of ILK/mTOR signaling complexes in migrating cells, as well as intracellular live imaging to follow dynamic changes in protein interactions involving these two proteins.     


Regulation of cell adhesion and signaling by the protein phosphatase, ILKAP
Project leader: Assoc Prof Greg Hannigan
Phone: 9594 7245

Integrin linked kinase, ILK, is an effector of phosphoinositide 3’-OH kinase (PI3K) signaling, which is commonly activated and contributes to cancer progression due to genetic loss of the PI3K inhibitor PTEN. Thus, the PTEN tumor suppressor normally antagonizes ILK signaling. Accordingly, ILK activity is often elevated in cancers including breast, prostate, lung, gastric and colon carcinomas. We have found that oncogenic ILK signaling is also inhibited by the protein phosphatase ILKAP, which interacts directly with ILK. Our analysis of human cancers indicates that ILKAP protein levels are often markedly reduced or undetectable in glioblastoma, an aggressive brain tumour, suggesting a novel mechanism of ILK activation in cancer.

The project will investigate the interaction of ILK and ILKAP, with an eye toward understanding how ILK signaling is normally regulated by the activity of this phosphatase. Our work indicates that ILKAP activity does not completely inhibit cellular ILK signaling, and this selectivity may involve differential subcellular localization of ILK-ILKAP complexes. Molecular, biochemical and live imaging studies of ILKAP and its associated proteins will be undertaken to elucidate the mode of ILKAP regulation of ILK signaling.