Changes in the expression of the potassium channels TASK1, TASK3 and TRESK in a rat model of oral squamous cell carcinoma and their relation to malignancy

Publication date: Available online 16 February 2019

Source: Archives of Oral Biology

Author(s): Walther D. Zavala, Mabel R. Foscolo, Patricia E. Kunda, Juan C. Cavicchia, Cristian G. Acosta

Abstract

Objectives

Potassium channels have been proposed to promote cancer cell proliferation and metastases. Thus, we investigated the expression pattern of three 2-pore domain potassium channels (K2 Ps) TASK1, TASK3 and TRESK in advanced oral squamous cell carcinoma (OSCC), the commonest oral malignancy.

Design

We used 4-nitroquinoline-1-oxide (4-NQO) to induce high grade OSCC in male adult rats. We then used immunohistochemistry and Western blotting to study the distribution and expression pattern of TASK1, TASK3 and TRESK in normal versus cancerous tissue. We also examined the expression of β-tubulin III (β-tub3), a marker associated with resistance to taxane-based chemotherapy and poor patient prognosis, and its correlation with the K2 Ps. Finally, we studied the expression of TASK1, TASK3 and TRESK in human samples of SCC of oral origin.

Results

We found that TASK3 was significantly up-regulated whereas TASK1 and TRESK were both significantly down-regulated in advanced, poorly differentiated OSCC. Both, rat and human SCC showed a significant increase in the expression of β-tub3. Interestingly, the expression of the latter correlated positively and significantly with TASK3 and TRESK but not TASK1 in rat OSCC. Our initial results showed a similar pattern of up and down regulation and correlation with β-tub3 for these three K2 Ps in human SCC.

Conclusions

The changes in expression and the co-localization with a marker of resistance to taxanes like β-tub3 turn TASK1, TASK3 and TRESK into potentially new prognostic tools and possibly new therapeutic targets for OSCC.

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