Human thyroid cancer is the most commonly occurring cancer of the endocrine gland having good survival rate, but some patients show recurrence with an invasive phenotype and treatment failures. The mechanisms behind this invasive phenotype are not well understood in TC. Previously our group has identified a pro-migratory role of relaxin-like peptides in thyroid cancer that is mediated by S100A4. We have observed in human TC cells that extracellular S100A4 induces migration and activates ERK1/2, JNK/SAPK and NFkB signaling pathways. Employing immunohistochemistry and immunofluorescence we have identified the expression of RAGE in human TC primary cells, cell lines, and in tumor tissues but not in normal thyroid tissues. We showed that S100A4 binds to RAGE in TC cells and that RAGE and its cytoplasmic partner Dia-1 mediate the S100A4-induced migration of TC cells. This study identified a crucial role of RAGE in TC cell migration induced by S100A4.

Human thyroid cancer is the most commonly occurring cancer of the endocrine gland having good survival rate, but some patients show recurrence with an invasive phenotype and treatment failures. The mechanisms behind this invasive phenotype are not well understood in TC. Previously our group has identified a pro-migratory role of relaxin-like peptides in thyroid cancer that is mediated by S100A4. We have observed in human TC cells that extracellular S100A4 induces migration and activates ERK1/2, JNK/SAPK and NFkB signaling pathways. Employing immunohistochemistry and immunofluorescence we have identified the expression of RAGE in human TC primary cells, cell lines, and in tumor tissues but not in normal thyroid tissues. We showed that S100A4 binds to RAGE in TC cells and that RAGE and its cytoplasmic partner Dia-1 mediate the S100A4-induced migration of TC cells. This study identified a crucial role of RAGE in TC cell migration induced by S100A4.