title: Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer.
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.
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, London, UK.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Todd
authors.affiliation: Department of Medicine, Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Ryall
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Vyse
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, London, UK.
authors.forename: Jocelyn P
authors.initials: JP
authors.lastname: Wong
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.|Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
authors.forename: Rachael C
authors.initials: RC
authors.lastname: Natrajan
authors.affiliation: Division of Molecular Pathology, The Institute of Cancer Research, London, UK.
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Translational Bioinformatics and Cancer Systems Biology Laboratory, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Aik-Choon
authors.initials: AC
authors.lastname: Tan
authors.affiliation: Division of Cancer Biology, The Institute of Cancer Research, London, UK.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Huang
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D002448:Cell Adhesion; D049109:Cell Proliferation; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D007797:Laminin / Q000378:metabolism; D009362:Neoplasm Metastasis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007797:Laminin; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: HER2; breast cancer; cell adhesion; extracellular matrix; laminin