title: Annexin A2 in renal cell carcinoma: expression, function, and prognostic significance.
abstract: OBJECTIVE
  Renal cell carcinoma (RCC) is the most lethal genitourinary cancer and intrinsically resistant to chemotherapy, radiotherapy, and hormone therapy. Annexin A2 (Anxa2) is a calcium-dependent phospholipid-binding protein found on various cell types that plays multiple roles in regulating cellular functions. In RCC, Anxa2 expression was correlated with tumor differentiation, clinical outcomes, and the metastatic potential; however, the underlying mechanisms remain obscure. This study investigated the role of Anxa2 in regulating tumorigenesis of RCC.
  
  
  METHODS
  Commercial RCC tissue microarray arrays and a kidney cancer quantitative polymerase chain reaction array were used to examine Anxa2 by immunohistochemistry and real-time polymerase chain reaction analysis. Short hairpin (sh)RNA-based lentiviral system technology was used to evaluate the effects of manipulating Anxa2 expression on multiple malignant features of 2 RCC cell lines, A498 and 786-O, and its mechanisms.
  
  
  RESULTS
  (1) The Anxa2 expression level was generally elevated to varying degrees in RCC tissues. In adjacent noncancerous tissues, Anxa2 was mainly expressed in glomeruli and slightly expressed in the cytoplasm of proximal tubules. (2) An increased Anxa2 expression level was found in tissues of clear cell RCC, papillary RCC, and chromophobe RCC, and it was prominently expressed in cancer cell membranes. In addition, the Anxa2 expression level was correlated with poor prognosis. (3) Silencing Anxa2 expression suppressed the abilities of cell migration and invasion, but cell proliferation was less affected. (4) Diminished Anxa2 expression caused alterations in the cell polarity, disrupted the formation of actin filaments, and reduced CXCR4 expression. (5) Inhibition of the Rho/Rock axis restored silencing of Anxa2-mediated suppression of cell motility.
  
  
  CONCLUSIONS
  Overall, our study points out the regulatory function of Anxa2 in RCC cell motility and provides a molecular-based mechanism of Anxa2 positivity in the progression of RCC.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Han-Lin
authors.initials: HL
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Tai-Kuang
authors.initials: TK
authors.lastname: Chao
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Hsiao
authors.affiliation: School of Medical Laboratory Sciences and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan. Electronic address: ccheng@tmu.edu.tw.
authors.forename: Chao-Wen
authors.initials: CW
authors.lastname: Cheng
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000096:biosynthesis; D017306:Annexin A2 / Q000096:biosynthesis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015854:Up-Regulation
chemical_list: C472822:ANXA2 protein, human; D000199:Actins; D017306:Annexin A2
keywords: Actin cytoskeleton; Annexin A2; Cell motility; Metastasis; Rho GTPase