title: Increased expression levels of WAVE3 are associated with the progression and metastasis of triple negative breast cancer.
abstract: BACKGROUND
  Breast Cancer (BC) is a heterogeneous disease comprised of at least five genetically distinct subtypes, which together form the second leading cause of cancer death in women in the United States. Within BC subtypes, those classified as Triple Negative BCs (TNBCs) exhibit dismal survival rates due to their propensity to develop distant metastases. We have identified the WAVE3 protein, which is a critical regulator of actin cytoskeleton dynamics that are required for the motility and invasion of cancer cells through its activation of the Arp2/3 complex, as a key regulator of the different steps of the invasion-metastasis cascade in BC, especially in the more aggressive TNBCs. Our published studies have also shown that elevated expression levels of WAVE3 in the TNBC cell lines directly contribute to their increased invasion and metastasis potentials both in vitro and in vivo in murine models of BC metastasis.
  
  
  RESULTS
  Herein, we utilized both immunohistochemistry (IHC) of primary human BC tumors as well as quantitative real-time RT-PCR of WAVE3 in the peripheral blood of BC patients to clearly establish that WAVE3 is a predictive marker of overall BC patients' survival. High levels of WAVE3 were predictive for reduced distant recurrence-free survival as well as for decreased disease-specific mortality. Our analysis of WAVE3 expression levels in the peripheral blood of BC patients showed that WAVE3 is highly expressed in the blood of patients who developed metastatic breast cancer compared to those who did not. WAVE3 expression was also highly upregulated in the blood of BC patients with the more aggressive TNBC subtype.
  
  
  CONCLUSIONS
  Together, these findings establish WAVE3 as a novel marker for increased risk of breast-cancer-specific mortality and for the metastatic potential of the TNBCs, and also identify WAVE3 as an attractive therapeutic target for the treatment of metastatic BC.
authors.affiliation: Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois, United States of America. skulkarni@surgery.bsd.uchicago.edu
authors.forename: Swati
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Augoff
authors.forename: Louis
authors.initials: L
authors.lastname: Rivera
authors.forename: Brian
authors.initials: B
authors.lastname: McCue
authors.forename: Thaer
authors.initials: T
authors.lastname: Khoury
authors.forename: Adrienne
authors.initials: A
authors.lastname: Groman
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.forename: Khalid
authors.initials: K
authors.lastname: Sossey-Alaoui
mesh_terms: D000199:Actins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction / Q000379:methods; D012008:Recurrence; D016896:Treatment Outcome; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000096:biosynthesis*
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; C120153:WASF3 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family