Abstract
Expression of keratin (K) 13 is replaced with that of K17 when squamous cells of the oral mucosa transform from normal and dysplastic epithelia to carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Since 14-3-3 sigma is functionally associated with K17, we examined possible relationships between expression of K17 and 14-3-3 sigma in oral CIS and SCC tissues by immunohistochemistry. We furthermore examined whether or not K17 expression or knockdown by small interfering RNA (siRNA) modulates the behavior of SCC cells in culture in terms of cell proliferation and migration. In tissue specimens of oral SCC and CIS, the pattern of cytoplasmic expression of 14-3-3 sigma and K17 was similar but neither was expressed in normal or dysplastic epithelia. Both proteins were demonstrated in the cytoplasm of control oral SCC ZK-1 cells, but expression of 14-3-3 sigma changed from cytoplasmic to nuclear upon knockdown of K17. In carcinoma cells, therefore, cytoplasmic localization of 14-3-3 sigma seems to accompany expression of K17. In K17-knockdown cells, proliferation was significantly suppressed at 4 days after seeding. In addition, the cell size of K17-knockdown cells was significantly smaller than that of control cells; as a result of which in the migration experiments, we found delayed closure of scratch wounds but migration as such was not affected. We conclude that K17 expression promotes SCC cell growth and cell size but does not affect cell migration. K17 expression is accompanied by cytoplasmic expression of 14-3-3 sigma, indicative of their functional relationship.
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Acknowledgments
This work was supported in part by Grants-in-Aid for Scientific Research (to SM, JC, and TS) and for Young Scientists (to TM and SM) from the Japan Society for the Promotion of Science and by a grant for the Promotion of Niigata University Research Projects (to TM and SM).
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Unusual case of moderate epithelial dysplasia case positive for 14-3-3 sigma. (a) H&E stain, immunoperoxidase stains for 14-3-3 sigma (b), K17 (c), K13 (d), and Ki-67 (e), hematoxylin counterstain. a: × 200; b-e: × 300. In five cases of epithelial dysplasia (a), 14-3-3 sigma was weakly positive in the whole epithelial layer (b), while no staining for K17 (c) was noted. K13 was occasionally positive in the prickle cell layer (d), and Ki-67-positive cells were sporadically detected only in the second basal layer (e). This pattern of marker expression is characteristic for moderate dysplasia. (PDF 177 kb)
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Mikami, T., Maruyama, S., Abé, T. et al. Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration. Virchows Arch 466, 559–569 (2015). https://doi.org/10.1007/s00428-015-1735-6
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DOI: https://doi.org/10.1007/s00428-015-1735-6