Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer

Abstract

// Jason R. Todd 1,* , Karen A. Ryall 2,* , Simon Vyse 1,* , Jocelyn P. Wong 1 , Rachael C. Natrajan 3,4 , Yinyin Yuan 4 , Aik-Choon Tan 2 and Paul H. Huang 1 1 Division of Cancer Biology, The Institute of Cancer Research, London, UK 2 Department of Medicine, Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA 3 The Breast Cancer Now Toby Robins Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, UK 4 Division of Molecular Pathology, The Institute of Cancer Research, London, UK * These authors have contributed equally to this work Correspondence to: Paul H. Huang, email: // Keywords : cell adhesion, breast cancer, extracellular matrix, laminin, HER2 Received : March 22, 2016 Accepted : July 27, 2016 Published : August 17, 2016 Abstract Tumour cell-extracellular matrix (ECM) interactions are fundamental for discrete steps in breast cancer progression. In particular, cancer cell adhesion to ECM proteins present in the microenvironment is critical for accelerating tumour growth and facilitating metastatic spread. To assess the utility of tumour cell-ECM adhesion as a means for discovering prognostic factors in breast cancer survival, here we perform a systematic phenotypic screen and characterise the adhesion properties of a panel of human HER2 amplified breast cancer cell lines across six ECM proteins commonly deregulated in breast cancer. We determine a gene expression signature that defines a subset of cell lines displaying impaired adhesion to laminin. Cells with impaired laminin adhesion showed an enrichment in genes associated with cell motility and molecular pathways linked to cytokine signalling and inflammation. Evaluation of this gene set in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort of 1,964 patients identifies the F12 and STC2 genes as independent prognostic factors for overall survival in breast cancer. Our study demonstrates the potential of in vitro cell adhesion screens as a novel approach for identifying prognostic factors for disease outcome.