title: Targeting filamin A reduces K-RAS-induced lung adenocarcinomas and endothelial response to tumor growth in mice.
abstract: BACKGROUND
  Many human cancer cells express filamin A (FLNA), an actin-binding structural protein that interacts with a diverse set of cell signaling proteins, but little is known about the biological importance of FLNA in tumor development. FLNA is also expressed in endothelial cells, which may be important for tumor angiogenesis. In this study, we defined the impact of targeting Flna in cancer and endothelial cells on the development of tumors in vivo and on the proliferation of fibroblasts in vitro.
  
  
  METHODS
  First, we used a Cre-adenovirus to simultaneously activate the expression of oncogenic K-RAS and inactivate the expression of Flna in the lung and in fibroblasts. Second, we subcutaneously injected mouse fibrosarcoma cells into mice lacking Flna in endothelial cells.
  
  
  RESULTS
  Knockout of Flna significantly reduced K-RAS-induced lung tumor formation and the proliferation of oncogenic K-RAS-expressing fibroblasts, and attenuated the activation of the downstream signaling molecules ERK and AKT. Genetic deletion of endothelial FLNA in mice did not impact cardiovascular development; however, knockout of Flna in endothelial cells reduced subcutaneous fibrosarcoma growth and vascularity within tumors.
  
  
  CONCLUSIONS
  We conclude that FLNA is important for lung tumor growth and that endothelial Flna impacts local tumor growth. The data shed new light on the biological importance of FLNA and suggest that targeting this protein might be useful in cancer therapeutics.
authors.affiliation: Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Sahlgrenska Academy, SE-405 30, Göteborg, Sweden.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Nallapalli
authors.forename: Mohamed X
authors.initials: MX
authors.lastname: Ibrahim
authors.forename: Alex X
authors.initials: AX
authors.lastname: Zhou
authors.forename: Sashidar
authors.initials: S
authors.lastname: Bandaru
authors.forename: Sai Naresh
authors.initials: SN
authors.lastname: Sunkara
authors.forename: Björn
authors.initials: B
authors.lastname: Redfors
authors.forename: David
authors.initials: D
authors.lastname: Pazooki
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
authors.forename: Martin O
authors.initials: MO
authors.lastname: Bergo
authors.forename: Levent M
authors.initials: LM
authors.lastname: Akyürek
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D003285:Contractile Proteins / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005354:Fibrosarcoma / Q000235:genetics; D064448:Filamins; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D018390:Gene Targeting; D011905:Genes, ras; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000235:genetics
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins