title: Filamin A expression correlates with proliferation and invasive properties of human metastatic melanoma tumors: implications for survival in patients.
abstract: OBJECTIVE
  Filamin A (FLNa) cross-links actin filaments into dynamic orthogonal networks and interacts with binding proteins of diverse cellular functions that are implicated in cell growth and motility regulation. Here, we tested the hypothesis that FLNa plays a role in cancer proliferation and metastasis via the regulation of epidermal growth factor receptor (EGFR) function.
  
  
  METHODS
  Ectopic expression and knockdown of FLNa in human melanoma cell lines was performed to investigate changes in cellular proliferation, migration and invasion in vitro and tumor growth in a xenograft model in the mouse. The role of FLNa in EGFR expression and signaling was evaluated by Western blot. Immunohistochemistry was performed on histological sections of human melanoma tumors to determine whether an association existed between FLNa and overall survival.
  
  
  RESULTS
  The depletion of FLNa significantly reduced the proliferation, migration and invasion of two melanoma cell lines in vitro and was associated with smaller tumors in a xenograft model in vivo. EGF-induced phosphorylation of EGFR and activation of the Raf-MEK-ERK cascade was negatively affected by the silencing of FLNa both in vitro and in vivo. Cancer patients with low melanoma tumor FLNa expression have improved survival benefit.
  
  
  CONCLUSIONS
  These data indicate that enhanced tumorigenesis occurs through increase in EGF-induced EGFR activation in FLNa-expressing melanoma cells and that high FLNa levels are predictors of negative outcome for patients with melanoma tumors.
authors.affiliation: Department of Oncology, Hebei Medical University, Shijiazhuang, 050017, Hebei, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Tienian
authors.initials: T
authors.lastname: Zhu
authors.forename: Dongmei
authors.initials: D
authors.lastname: Gao
authors.forename: Yimei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qinglan
authors.initials: Q
authors.lastname: Zhao
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Tongyi
authors.initials: T
authors.lastname: Su
authors.forename: Michel
authors.initials: M
authors.lastname: Bernier
authors.forename: Ruijing
authors.initials: R
authors.lastname: Zhao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D064448:Filamins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden
chemical_list: D064448:Filamins; C512478:EGFR protein, human; D066246:ErbB Receptors