HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer
Vineesh Indira Chandran1, Serenella Eppenberger-Castori2, Thejaswini Venkatesh3, Kara Lea Vine4,5,6, Marie Ranson4,5,6
1 Department of Clinical Sciences, Section of Oncology and Pathology, Lund University, Lund, Sweden.
2 Institute for Pathology, Department of Molecular Pathology, Schoenbeinstrasse, Basel, Switzerland.
3 Nitte University Centre for Science Education and Research (NUCSER), K. S. Hegde Medical Academy, Nitte University, Deralakatte, Mangalore, Karnataka, India.
4 School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia.
5 Centre for Medical & Molecular Bioscience, University of Wollongong, Wollongong, NSW, Australia.
6 Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Vineesh Indira Chandran, email:
Keywords: HER2/ERBB2, uPAR/PLAUR, HER2-positive breast cancer, co-overexpression, co-amplification, correlation
Received: January 20, 2015 Accepted: March 16, 2015 Published: March 23, 2015
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.