Expression of Ribosomal Protein S6 Kinase (S6K1) Isoforms in Different Types of Papillary Thyroid Carcinoma

Ribosomal protein kinase S6 (S6K1) is one of the key components of the PI3K/mTOR/S6K1-dependent signaling cascade, which plays an important role in the regulation of translation, cell growth, survival, proliferation, and cell migration. Disturbances in the functioning of the PI3K/mTOR/S6K1 signaling cascade, in particular changes in the expression and activity of S6K1, accompany the development of a number of human pathologies, including oncological, neurodegenerative, and cardiovascular diseases; metabolic disorders; and pathologies associated with aging. Recently, in addition to the already known p70 and p85, the existence of a new isoform of the S6K1 kinase, p60, was confirmed. In addition, it was established that a change in the balance in the expression of various S6K1 isoforms towards an increase in p60-S6K1 leads to a multiple increase in the motility of model malignant cells, which is accompanied by significant changes in the expression of molecules involved in cell adhesion and intercellular interaction and may indicate that the cells acquire tumor characteristics important for invasion and metastasis. To find out whether the expression of the p60 isoform of S6K1 correlates with invasion and metastasis at the tumor level, the expression level of S6K1 isoforms was analyzed in three groups of human papillary thyroid carcinoma tumors, namely, without signs of invasion, with signs of invasion, and with lymph node metastases. Conditionally normal tissues adjacent to the tumors were also analyzed at the same time. The analysis was carried out by real-time PCR. A trend towards an increase in the expression level of all S6K1 isoforms, as well as the p60 isoform of S6K1 in tumors with manifestations of invasion and metastasis, was established. However, changes in the ratio of the total expression level of all S6K1 isoforms to p60-S6K 1 in the direction of an increase in the share of the latter in tumors with manifestations of metastasis turned out to be statistically reliable. The obtained results indicate an important role of the p60S6K1 isoform in the maintenance or initiation of invasion and metastasis of thyroid tumors.