Coordinated expression of keratin17 and 14-3-3 sigma regulates in cell proliferation and migration of oral squamous cell carcinoma

Background and objective: We have reported reciprocal switching in the keratin (K) subtype expression from K13 to K17 occurs during malignant transformation of the oral mucosa from normal and dysplastic epithelia to carcinoma in-situ (CIS) and squamous cell carcinoma (SCC) (Oral Oncology 2011;47:497–503). Since 14-3-3 sigma, an adaptor protein, is known to behave in association with K17, we investigated behaviors of these two molecules in oral CIS and SCC to elucidate the keratin switching mechanism.

Methods: We determined immunohistochemical profiles of 14-3-3 sigma in comparison with those of K17 in surgical tissue specimens of oral borderline malignancies and SCC as well as in ZK-1, an oral SCC cell system. In addition, to study functional roles of K17 in carcinoma cells, we examined cell proliferation and migration and intracellular behaviours of 14-3-3 sigma in ZK-1 cells when their K17 gene expressions were suppressed by transient knockdown using K17-siRNA (K17-siRNA cells).

Results: Both 14-3-3 sigma and K17 were similarly expressed in the cytoplasm of oral SCC and CIS cells but not in normal or dysplastic epithelia at tissue levels. They both were demonstrated in the cytoplasm of control ZK-1 cells, while 14-3-3 sigma was converted from the cytoplasm into the nucleus in K17-siRNA cells. The proliferation of K17-siRNA cells was significantly suppressed on and after day 4 after seeding. In addition, they migrated obviously slower in scratch wound assays. Thus, the cytoplasmic location of 14-3-3 sigma seemed to be in parallel to the emerge of K17 in carcinoma cells.

Conclusion: The results indicate that the K17 expression play an important role in promoting carcinoma cell growth in association with 14-3-3 sigma by regulating its adaptor functions.

Key words: oral squamous cell carcinoma; carcinoma in-situ; keratin 17; 14-3-3 sigma; siRNA

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Jan 21, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Coordinated expression of keratin17 and 14-3-3 sigma regulates in cell proliferation and migration of oral squamous cell carcinoma
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