title: Upregulated Annexin A1 promotes cellular invasion in triple-negative breast cancer.
abstract: Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. While many studies have investigated the ANXA1 expression in various tumor types, the role of ANXA1 is not fully understood. Therefore, in the present study, we evaluated the ANXA1 expression in 211 breast cancer patients and compared the levels with clinicopathological factors. ANXA1 was positively expressed in 31 (14.7%) of the 211 cases in our cohort, and these positive cases were associated with triple-negative breast cancer (TNBC) (P=0.007) and venous invasion (P=0.028). The in vitro cell experiment found that the MDA-MB-231 cell line, which is a TNBC cell line, highly expressed ANXA1. Using this cell line, the functional role of ANXA1 in breast cancer was revealed and the knockdown of ANXA1 by specific siRNA demonstrated a significant reduction in cellular invasion. Further experiments indicated that ANXA1 was induced by hypoxia with hypoxia-inducible factor-1α induction. These results suggested that ANXA1, which enhanced breast cancer invasion and metastasis under hypoxia, were significantly associated with the worst patient outcome. This is particularly noted in TNBC, the group of breast cancer with the worst outcome for which new therapeutic implications are required.
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Okano
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kumamoto
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Onozawa
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Katsuharu
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Abe
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohtake
authors.affiliation: Department of Organ Regulatory Surgery, Fukushima Medical University School of Medicine, Fukushima 960‑1295, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Takenoshita
mesh_terms: D017305:Annexin A1 / Q000096:biosynthesis*; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D017305:Annexin A1; D034741:RNA, Small Interfering