Dual contribution of MAPK and PI3K in epidermal growth factor-induced destabilization of thyroid follicular integrity and invasion of cells into extracellular matrix
| Autor: | Camilla Ingeson-Carlsson, Mikael Nilsson |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Cell Survival MAP Kinase Signaling System Swine Morpholines Thyroid Gland Biology Extracellular matrix Tissue Culture Techniques Phosphatidylinositol 3-Kinases Epidermal growth factor Cell Movement Internal medicine Nitriles medicine Butadienes Animals Neoplasm Invasiveness Thyroid Neoplasms Enzyme Inhibitors Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Epidermal Growth Factor Kinase Thyroid Cell migration Cell Biology Cell biology Extracellular Matrix Endocrinology medicine.anatomical_structure Chromones hormones hormone substitutes and hormone antagonists |
| Zdroj: | Experimental cell research. 326(2) |
| ISSN: | 1090-2422 |
| Popis: | Normal thyrocytes grown as reconstituted follicles in collagen gel were evaluated for drug effects of small molecule kinase inhibitors on growth factor-induced cell migration in a 3D context. MEK inhibition by U0126 only partially antagonized EGF/serum-induced cell migration from the basal follicular surface into the matrix. Combined treatment with U0126 and LY294002, a PI3K blocker, was necessary to abolish migration. However, exposure to only LY294002 facilitated the response to EGF by breakdown of the original follicular structure. In the same time EGF promoted thyroid cell survival that was compromised by LY294002 in absence of EGF. Cells treated with EGF and LY294002 retained the ability to form follicles. The findings indicate that dual inhibition of MAPK and PI3K/AKT pathways is required to fully block matrix invasion of EGF-stimulated thyroid cells. Conversely, single drug treatment with PI3K inhibitor adversely promotes invasiveness probably by destabilizing the follicular epithelium. |
| Databáze: | OpenAIRE |
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