title: 1α,25(OH)2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1.
abstract: BACKGROUND
  Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1), p21 protein-activated kinase 1 (PAK1) and actin related protein 2 (ARP2). Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH)2D3), a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH)2D3 modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line.
  
  
  METHODS
  To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting.
  
  
  RESULTS
  A 24 hour treatment with 1α,25(OH)2D3 (100 nM) significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH)2D3 on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1.
  
  
  CONCLUSIONS
  1α,25(OH)2D3 leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zeng
authors.forename: Madhuri S
authors.initials: MS
authors.lastname: Salker
authors.forename: Shaqiu
authors.initials: S
authors.lastname: Zhang
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Singh
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
authors.forename: Christos
authors.initials: C
authors.lastname: Stournaras
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D051377:Actin-Related Protein 2 / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D058105:Polymerization / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: C495926:ACTR2 protein, human; D051377:Actin-Related Protein 2; D000199:Actins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; C515903:PAK1 protein, human; D054462:p21-Activated Kinases; D020830:rac1 GTP-Binding Protein