S100A4 signaling in thyroid cancer

Abstract

Thyroid cancer (TC) is one of the most frequently occurring cancers of endocrine glands in Canada and the United States. Most differentiated TC are curable, but some TCs develop a more aggressive phenotype with resulting metastasis and treatment failures. Our group has shown that relaxin‐like peptides promote TC cell tumor growth and migration, in part mediated via S100A4 which is known to promote metastasis and to confer poor prognosis in patients with TC. Several S100 proteins signal via receptor for advanced glycation end products (RAGE). This study investigates S100A4 signaling in promoting TC cell survival, growth and metastasis. TC cells were stimulated with S100A4 to determine cell motility, proliferation and apoptosis and to identify S100A4‐induced signaling pathways. Using PCR and immunohistochemistry expression of RAGE was detected in TC cells and in TC tissues, but not in normal thyroid tissues. RAGE pull‐down experiments demonstrated S100A4 to bind to RAGE in TC. ERK and JNK/SAPK signaling pathways were activated in TC cells upon S100A4 stimulation. We used RAGE blocking antibodies and diaphanous‐1 knock‐down to prevent RAGE‐mediated S100A4‐signaling in TC. S100A4‐induced ERK‐signaling appeared to be independent of RAGE in TC. We identified TLR4 expression in TC cells and demonstrate here that the effects of S100A4 are, in part, mediated via TLR4 in TC. This research is funded by NSERC of Canada and Dept of surgery research fund.Grant Funding Source: n/a