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

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

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

Автор(и)

В. Г. Хоперія Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ, Ukraine
О. С. Ларін Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ, Ukraine https://orcid.org/0000-0002-5090-5110
В. В. Васько Педіатричний факультет Університету силових структур, Бетезда (США), United States

DOI:

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

Ключові слова:

thyroid, cancer, E-cadherin, methylation, metastasis

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.

Біографії авторів

В. Г. Хоперія, Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ

V. Khoperia

О. С. Ларін, Український науково-практичний центр ендокринної хірургії, трансплантації ендокринних органів і тканин МОЗ України, Київ

O. Larin

В. В. Васько, Педіатричний факультет Університету силових структур, Бетезда (США)

V. Vasko

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