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Migration and invasion of oral squamous carcinoma cells is promoted by WNT 5A, a regulator of cancer progression
Author(s) -
Prgomet Zdenka,
Axelsson Lena,
Lindberg Pia,
Andersson Tommy
Publication year - 2015
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12292
Subject(s) - regulator , wnt signaling pathway , cancer research , cancer , squamous carcinoma , basal cell , metastasis , carcinoma , medicine , chemistry , biology , pathology , microbiology and biotechnology , biochemistry , signal transduction , gene
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 WNT 5A 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 WNT 5A expression by Western blot, whereas WNT5A‐induced responses were analyzed by measuring calcium (Ca 2+ ) signaling , PKC activation, migration and invasion. Results Despite the lack of WNT 5A expression, both cell lines responded to recombinant WNT 5A (r WNT 5A) with activation of the non‐canonical WNT /Ca 2+ / PKC pathway. This effect was ascertained to be mediated by WNT 5A by use of the WNT 5A antagonist, Box5. To investigate how WNT 5A affects tumor progression, r WNT 5A‐induced alterations in BrdU absorbance (reflecting the number of tumor cells) were analyzed. r WNT 5A had no effect on BrdU absorbance but instead promoted tumor cell migration and invasion. These results were confirmed by the use of the WNT 5A‐mimicking peptide Foxy5, while the rWNT5A‐induced migration was blocked by secreted Frizzled‐related protein 1 ( SFRP 1), protein kinase C inhibitors or the intracellular Ca 2+ chelator, MAPT . Conclusions These novel data clearly show that WNT 5A activates the non‐canonical WNT /Ca 2+ / 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 .