title: Annexin A1 Preferentially Predicts Poor Prognosis of Basal-Like Breast Cancer Patients by Activating mTOR-S6 Signaling.
abstract: BACKGROUND
  Annexin A1 (ANXA1) is an anti-inflammatory protein reported to play a role in cell proliferation and apoptosis, and to be deregulated in breast cancer. The exact role of annexin A1 in the biology of breast cancer remains unclear. We hypothesized that the annexin A1 plays an oncogenic role in basal subtype of breast cancer by modulating key growth pathway(s).
  
  
  METHODS
  By mining the Cancer Genome Atlas (TCGA)-Breast Cancer dataset and manipulating annexin A1 levels in breast cancer cell lines, we studied the role of annexin A1 in breast cancer and underlying signaling pathways.
  
  
  RESULTS
  Our in-silico analysis of TCGA-breast cancer dataset demonstrated that annexin A1 mRNA expression is higher in basal subtype compared to luminal and HER2 subtypes. Within the basal subtype, patients show significantly poorer overall survival associated with higher expression of annexin A1. In both TCGA patient samples and cell lines, annexin A1 levels were significantly higher in basal-like breast cancer than luminal and Her2/neu-positive breast cancer. Stable annexin A1 knockdown in TNBC cell lines suppressed the mTOR-S6 pathway likely through activation of AMPK but had no impact on the MAPK, c-Met, and EGFR pathways. In a cell migration assay, annexin A1-depleted TNBC cells showed delayed migration as compared to wild-type cells, which could be responsible for poor patient prognosis in basal like breast cancers that are known to express higher annexin A1.
  
  
  CONCLUSIONS
  Our data suggest that annexin A1 is prognostic only in patients with basal like breast cancer. This appears to be in part due to the role of annexin A1 in activating mTOR-pS6 pathway.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Anjana
authors.initials: A
authors.lastname: Bhardwaj
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Nivetha
authors.initials: N
authors.lastname: Ganesan
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Kazunoshin
authors.initials: K
authors.lastname: Tachibana
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Kimal
authors.initials: K
authors.lastname: Rajapakshe
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Albarracin
authors.affiliation: Department of Biology and Biochemistry, University of Houston, Houston, TX, United States of America.
authors.forename: Preethi H
authors.initials: PH
authors.lastname: Gunaratne
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America.
authors.forename: Cristian
authors.initials: C
authors.lastname: Coarfa
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bedrosian
mesh_terms: D017305:Annexin A1 / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D003198:Computer Simulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018295:Neoplasms, Basal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D017305:Annexin A1; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases