Crosstalk between thyroid hormones, analogs and ligands of integrin αvβ3 in health and disease. Who is talking now?

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Background

Thyroid hormones, T3 and T4, have two distinct signaling pathways: a nongenomic signaling that involves a membrane receptor, such as integrin αvβ3, although the classical cytosolic/ nuclear receptor can also mediate the fast effects, taking place at the plasma membrane level or in the cytosol. The other signaling is the nuclear pathway mediated by the receptors α and β, depends on transcription factors and gives a slower response, involving protein synthesis. The integrin αvβ3 is a heterodimeric integral plasma membrane protein able to interact with the extracellular matrix proteins widely expressed in practically all cells, particularly in endothelial and cancer cells. The nongenomic and genomic pathways for both hormones may crosstalk, but at the same time there may be an overlapping of both thyroid and steroid signaling, able to bind the integrin and modulate physiopathological responses of the cell, such as tumor growth. In particular integrin β3 may modulate the balance between pro-tumor and anti-tumor signaling of immune cells via STAT signaling. Therefore, integrins appear a very interesting target of the immune microenvironment and may be good candidates for tumor immunotherapy.

The special Issue is aimed to better understand the possible role of interaction of Thyroid hormones with the integrin αvβ3, taking into account that this integrin can bind other small molecules with hormone function, such testosterone, estrogen as well as nutrients, resveratrol, and other stilbene derivatives together with their possible role in pathological situations such as cancer cell growth. Growth factors may also crosstalk with thyroid hormones and the possible implications and relevance for cancer therapy, and other physiopathological situations significantly affecting the world population at present days will be evaluated.
There are several aspects concerning the interaction of thyroid hormones with integrin αvβ3 and therefore of other possible ligands involved that could be studied in the light of the more recent literature.
T3 binds the integrin with lower affinity with respect to T4. Through the binding to integrin αvβ3, T4 is able to modulate the traffic of specific proteins in the cytosol (Estrogen receptor α, β-catenin, Hypoxic factor-1α, Thyroid Receptor, p53). It appears that many physiopathological functions are modulated by thyroid hormone, such as gene expression, cell proliferation, apoptosis and metastasis

The scope of this Special Issue is to shed some light on the role of thyroid hormones and their metabolites in physiopathological situations such as cancer, where tetraiodothyroacetic acid (tetrac), a metabolite of thyroid hormone, and a probe for integrin αvβ3, and its nano- derivatives, have shown promising results in cancer cell growth. Therefore the aims that will be addressed in the Special Issue are:
1. Role of tetrac, its nano-derivatives and metabolites of thyroid hormones in cancer cell growth;
2. Role of molecules also with hormone function, nutrients such as stilbene derivatives, able to bind integrin αvβ3 and modulate cell function;
3. Roles of integrin αvβ3 in the modulation of processes and factors that may be important for cancer cell proliferation: angiogenesis, deiodinases, hypothyroidism, irradiation;
4. Role of thyroid hormones in metabolic processes in health and disease;
5. Crosstalk of thyroid hormones with growth factors and its role in physiopathological situations;
6. Thyroid hormone, metabolites and immune function. Role of integrin αvβ3 in health and disease.

The papers included in the special issue should be preferentially either reviews or experimental papers.

Keywords: Integrin, Cancer, Immunotherapy, Tetrac, stilbene derivatives, diiodothyronines, αvβ3

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