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

Journal Article


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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


  •   Indira Chandran, Vineesh (external author)
  •   Eppenberger-Castori, Serenella (external author)
  •   Venkatesh, Thejaswini (external author)
  •   Vine, Kara L.
  •   Ranson, Marie

Publication Date


  • 2015

Citation


  • Indira Chandran, V., Eppenberger-Castori, S., Venkatesh, T., Vine, K. Lea. & Ranson, M. (2015). HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer. Oncoscience, 2 (3), 207-224.

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3827&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2806

Number Of Pages


  • 17

Start Page


  • 207

End Page


  • 224

Volume


  • 2

Issue


  • 3

Place Of Publication


  • http://www.impactjournals.com/oncoscience/index.php?abs=146

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


  •   Indira Chandran, Vineesh (external author)
  •   Eppenberger-Castori, Serenella (external author)
  •   Venkatesh, Thejaswini (external author)
  •   Vine, Kara L.
  •   Ranson, Marie

Publication Date


  • 2015

Citation


  • Indira Chandran, V., Eppenberger-Castori, S., Venkatesh, T., Vine, K. Lea. & Ranson, M. (2015). HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer. Oncoscience, 2 (3), 207-224.

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3827&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2806

Number Of Pages


  • 17

Start Page


  • 207

End Page


  • 224

Volume


  • 2

Issue


  • 3

Place Of Publication


  • http://www.impactjournals.com/oncoscience/index.php?abs=146