Роль експресії Е-кадгерину в процесі інвазії папілярного раку щитоподібної залози

В. Г. Хоперія, О. С. Ларін, В. В. Васько

Анотація


To determine whether the mesenchymal feature of invasive cancer cells is maintained in metastatic sites, we examined E-cadherin methylation and E-cadherin expression in 66 papillary thyroid cancer (PTC) samples and in 34 corresponding lymph node metastases (LNM). Hypermethylation of the E-cadherin gene promoter was detected in 39.3% of the PTCs, and loss of E-cadherin expression correlated with lymphocytic infiltration, extrathyroidal invasion and the presence of metastases. Comparing primary PTCs to the corresponding LNM, E-cadherin methylation status was identical in 60% of the cases. Loss of epigenetic silencing in LNMwas associated with a gain of E-cadherin expression. Hypermethylation of the E-cadherin gene promoter was detected in thyroid cancer cell lines with mesenchymal-like morphology. Loss of E-cadherin expression in these cells correlated with high migratory ability. Inhibition of RAS/ERK or PI3K/AKTsignaling decreased the migratory ability of these cells but did not induce E-cadherin expression. In the cells with epithelial-like morphology, treatments with phorbolester or tumor necrosis factor (TNF)-α resulted in translocation of membranous E-cadherin to the cytoplasm and induction of migration. E-cadherin promoter methylation status and E-cadherin expression were not affected by TNF. Together, dynamic changes in E-cadherin methylation occur during metastatic progression in thyroid cancer. Epigenetic mechanisms and TNF-inducible signaling independently contribute to the regulation of E-cadherin expression and localization. These mechanisms may play a role in the induction of EMTin primary tumors and in the conversion from the mesenchymal to the epithelial phenotype in metastases.


Ключові слова


thyroid; cancer; E-cadherin; methylation; metastasis

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Посилання


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DOI: https://doi.org/10.24026/1818-1384.1(38).2012.80958



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ISSN: 1818-1384 (Print), e-ISSN: 2519-2582, DOI: 10.24026/1818-1384.

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