Aki Manninen

Specific integrin functions in prostate cancer

A laminin-rich basement membrane orients the polarity of epithelial cells by serving as a ligand for members of the integrin family of ECM receptors. How the different integrins convey signals from the ECM into the cells is not thoroughly understood. Integrin-mediated signalling is perturbed in many different cancer types contributing to abnormal migration, invasion, proliferation and survival of tumour cells. Epithelial polarity is a critical regulator of oncogenesis and multiple polarity-related genes appear to function as tumour suppressors. In this project we study functional synergies or antagonisms between selected integrins in prostate cancer. 3D cultures of genetically engineered prostate epithelial cell lines as well as primary prostate organoids are used as a model system. Lentiviral vectors are used to overexpress (oncogenes) or knock out (CRISPR) selected prostate cancer associated genes. Our aim is to facilitate the development of novel targeted therapeutic approaches to inhibit malignant transformation by modulating reciprocal signalling between prostate cancer cells and their tumour-promoting microenvironment.