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HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer.

Indira Chandran, Vineesh LU ; Eppenberger-Castori, Serenella; Venkatesh, Thejaswini; Vine, Kara Lea and Ranson, Marie (2015) In Oncoscience 2(3). p.207-224
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Oncoscience
volume
2
issue
3
pages
207 - 224
publisher
Impact Journals
external identifiers
  • PMID:25897424
  • Scopus:84947616846
ISSN
2331-4737
language
English
LU publication?
yes
id
b95c106f-2d5e-48c9-a515-d9465ba66897 (old id 5341095)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25897424?dopt=Abstract
date added to LUP
2015-05-04 10:35:07
date last changed
2016-10-13 04:36:37
@misc{b95c106f-2d5e-48c9-a515-d9465ba66897,
  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.},
  author       = {Indira Chandran, Vineesh and Eppenberger-Castori, Serenella and Venkatesh, Thejaswini and Vine, Kara Lea and Ranson, Marie},
  issn         = {2331-4737},
  language     = {eng},
  number       = {3},
  pages        = {207--224},
  publisher    = {ARRAY(0x8512e88)},
  series       = {Oncoscience},
  title        = {HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer.},
  volume       = {2},
  year         = {2015},
}