Pharmacological suppression of the Ras/MAPK pathway in thyroid carcinoma cells can provoke opposite effects on cell migration and proliferation: The appearance of yin-yang effects and the need of combinatorial treatments

Glassmann,Alexander; Winter,Jochen; Kraus,Dominik; Veit,Nadine; Probstmeier,Rainer

doi:10.3892/ijo.2014.2668

Pharmacological suppression of the Ras/MAPK pathway in thyroid carcinoma cells can provoke opposite effects on cell migration and proliferation: The appearance of yin-yang effects and the need of combinatorial treatments

Authors:
- Alexander Glassmann
- Jochen Winter
- Dominik Kraus
- Nadine Veit
- Rainer Probstmeier
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Affiliations: Life Science Inkubator GmbH, Bonn, Germany, Oral Cell Biology Group, Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany, Department of Prosthodontics, Preclinical Education and Material Science, University of Bonn, Bonn, Germany, Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University Hospital of Bonn, Bonn, Germany
Published online on: September 23, 2014 https://doi.org/10.3892/ijo.2014.2668
Pages: 2587-2595

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Abstract

A major challenge in tumor therapy is the decrease or even the halting of cell proliferation and migration of cancerous cells. In the present study, we have analyzed the impact of a pharmacological blockade of the PI3K/Akt and MAPK/ERK1/2 signaling pathways on cell migration, proliferation and cell death in three human thyroid tumor cell lines that represent the main types of malignant thyroid carcinomas (B-CPAP, follicular; Cal-62, anaplastic; FTC-133, papillary thyroid carcinoma cells) and in which these pathways are constitutively activated. In general, pharmacological perturbation of PI3/Akt (application of MK-2206) and MEK/ERK1/2 (application of PD0325901 or U0126) signaling led to a cell line and drug-specific decrease in the proliferation and migration potential of thyroid carcinoma cells, although to a varying extent. However, one exception became apparent: in Cal-62 cells inhibition of the MEK/ERK1/2 module increased the migration rate up to 50%. This effect could be prevented by a simultaneous suppression of the PI3/Akt pathway, but also by application of the multiple kinase inhibitor sorafenib, a treatment that did not change the activation state of Akt. Thus, a pharmacological perturbation of canonical signaling pathways in thyroid carcinoma may induce drug-dependent yin-yang effects that are characterized by a simultaneous suppression of one (i.e., proliferation) and the activation of another (i.e., migration) cellular process. The appearance of such phenomena should be taken into account when therapy plans are established.

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