title: Migration and invasion of oral squamous carcinoma cells is promoted by WNT5A, a regulator of cancer progression.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) constitutes 90% of all cancers in the oral cavity, and the prognosis for patients diagnosed with OSCC is still poor. The identification of novel therapeutic targets and prognostic markers for OSCC is therefore essential. Previous studies of OSCC revealed an increased expression of WNT5A in the tumor tissue. However, no functional studies of WNT5A-induced effects in OSCC have been performed.
  
  
  METHODS
  Two different OSCC cell lines were used for analysis of WNT5A expression by Western blot, whereas WNT5A-induced responses were analyzed by measuring calcium (Ca²⁺) signaling, PKC activation, migration and invasion.
  
  
  RESULTS
  Despite the lack of WNT5A expression, both cell lines responded to recombinant WNT5A (rWNT5A) with activation of the non-canonical WNT/Ca²⁺ /PKC pathway. This effect was ascertained to be mediated by WNT5A by use of the WNT5A antagonist, Box5. To investigate how WNT5A affects tumor progression, rWNT5A-induced alterations in BrdU absorbance (reflecting the number of tumor cells) were analyzed. rWNT5A had no effect on BrdU absorbance but instead promoted tumor cell migration and invasion. These results were confirmed by the use of the WNT5A-mimicking peptide Foxy5, while the rWNT5A-induced migration was blocked by secreted Frizzled-related protein 1 (SFRP1), protein kinase C inhibitors or the intracellular Ca²⁺ chelator, MAPT.
  
  
  CONCLUSIONS
  These novel data clearly show that WNT5A activates the non-canonical WNT/Ca²⁺ /PKC pathway and increases migration and invasion of OSCC cells. This may indicate how an increased WNT5A expression in the tumor tissue is likely to promote progression of OSCC.
authors.affiliation: Oral Pathology, Faculty of Odontology, Malmö University, Malmö, Sweden.|Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Prgomet
authors.affiliation: Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Axelsson
authors.affiliation: Oral Pathology, Faculty of Odontology, Malmö University, Malmö, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Lindberg
authors.affiliation: Cell and Experimental Pathology, Department of Laboratory Medicine, Lund University, Clinical Research Centre, Skåne University Hospital, Malmö, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Andersson
mesh_terms: D015153:Blotting, Western; D020013:Calcium Signaling; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011379:Prognosis; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D000077195:Squamous Cell Carcinoma of Head and Neck; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000071818:Wnt-5a Protein; D016875:tau Proteins / Q000378:metabolism; D000099274:Frizzled-Related Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D016875:tau Proteins; D000099274:Frizzled-Related Proteins; C063306:HINT1 protein, human; C054369:MAPT protein, human; C085389:WNT5A protein, human
keywords: WNT5A; cell migration and invasion; oral squamous cell carcinoma