Tight junction protein ZO-1 as a possible marker of metastasis in thyroid carcinomas: a review of the literature and our own data

The plasticity of epithelial cells, exemplified by the epi­thelial-mesenchymal transition, has a crucial impact on tumorigenesis and metastasis. A key event in the epithelial-mesenchymal transition is the reorganization of intercellular junctions, especially tight junctions (TJ). TJ are areas of contact between epithe­lial and endothelial cells that create selective paracellular barriers that support body compartments. The TJ membrane is based on scaffolding, adaptor and signaling proteins. These include, in particular, the zonula occludens (ZO)-1–3 proteins, which create a scaffolding of TJ membrane proteins and influence the formation and dynamics of TJ strands, regulation and repair by connecting TJ to the cytoskeleton. ZO proteins are regulated by the nuclear factor kappa B signaling and cytokines. ZO proteins play impor­tant roles in embryonic development, tissue homeostasis, injury repair, inflammation, tumorigenesis, cancer progression, etc. The structural function ensures the barrier function of TJ, and the signal regulation function affects cell proliferation and motility. ZO proteins influence cell proliferation by moving between the nucleus and the membrane and regulating cell cycle-related proteins, such as cyclin D1 and proliferating cell nuclear antigen, and are considered tumor suppressors. It has been repeatedly proven that ZO proteins diffuse or are lost in almost all types of inflammation, during tumo­rigenesis, and metastasis. According to our data, ZO-1 is reduced in papillary carcinoma tumor tissue and metastases. Also, plasma level of ZO-1 in patients with papillary carcinoma is significantly lower than in the blood of healthy people. Thus, a decrease in the concentration of ZO-1 may be one of the markers of metastasis in thyroid carcinomas.