title: HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer.
abstract: Human epidermal growth factor receptor type 2 (HER2)-positive breast carcinoma is highly aggressive and mostly metastatic in nature though curable/manageable in part by molecular targeted therapy. Recent evidence suggests a subtype of cells within HER2-positive breast tumors that concomitantly expresses the urokinase plasminogen activator receptor (uPAR) with inherent stem cell/mesenchymal-like properties promoting tumor cell motility and a metastatic phenotype. This HER-positive/uPAR-positive subtype may be partially responsible for the failure of HER2-targeted treatment strategies. Herein we discuss and substantiate the cumulative preclinical and clinical evidence on HER2-uPAR cooperativity in terms of gene co-amplification and/or mRNA/protein co-overexpression. We then propose a regulatory signaling model that we hypothesize to maintain upregulation and cooperativity between HER2 and uPAR in aggressive breast cancer. An improved understanding of the HER2/uPAR interaction in breast cancer will provide critical biomolecular information that may help better predict disease course and response to therapy.
authors.affiliation: Department of Clinical Sciences, Section of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Vineesh
authors.initials: V
authors.lastname: Indira Chandran
authors.affiliation: Institute for Pathology, Department of Molecular Pathology, Schoenbeinstrasse, Basel, Switzerland.
authors.forename: Serenella
authors.initials: S
authors.lastname: Eppenberger-Castori
authors.affiliation: Nitte University Centre for Science Education and Research (NUCSER), K. S. Hegde Medical Academy, Nitte University, Deralakatte, Mangalore, Karnataka, India.
authors.forename: Thejaswini
authors.initials: T
authors.lastname: Venkatesh
authors.affiliation: School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia ; Centre for Medical & Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia ; Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Kara Lea
authors.initials: KL
authors.lastname: Vine
authors.affiliation: School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia ; Centre for Medical & Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia ; Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
authors.forename: Marie
authors.initials: M
authors.lastname: Ranson
keywords: HER2-positive breast cancer; HER2/ERBB2; co-amplification; co-overexpression; correlation; uPAR/PLAUR