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.

ZAVALA, WALTHER D.; FOSCOLO, MABEL R.; KUNDA, PATRICIA E.; CAVICCHIA, JUAN C.; ACOSTA CRISTIAN

ARCHIVES OF ORAL BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2019

0003-9969

Potassium channels have been proposed to promote cancer cell proliferation andmetastases. Thus, we investigated the expression pattern of three 2-pore domainpotassium channels (K2Ps) TASK1, TASK3 and TRESK in advanced oral squamous cellcarcinoma (OSCC), the commonest oral malignancy.DesignWe 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 andexpression pattern of TASK1, TASK3 and TRESK in normal versus cancerous tissue. Wealso examined the expression of -tubulin III (-tub3), a marker associated with resistanceto taxane-based chemotherapy and poor patient prognosis, and its correlation with theK2Ps. Finally, we studied the expression of TASK1, TASK3 and TRESK in humansamples of SCC of oral origin.ResultsWe found that TASK3 was significantly up-regulated whereas TASK1 and TRESK wereboth significantly down-regulated in advanced, poorly differentiated OSCC. Both, rat andhuman SCC showed a significant increase in the expression of -tub3. Interestingly, the expression of the latter correlated positively and significantly with TASK3 and TRESK butnot TASK1 in rat OSCC. Our initial results showed a similar pattern of up and downregulation and correlation with -tub3 for these three K2Ps in human SCC.ConclusionsThe changes in expression and the co-localization with a marker of resistance to taxaneslike -tub3 turn TASK1, TASK3 and TRESK into potentially new prognostic tools andpossibly new therapeutic targets for OSCC.