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首页> 外文期刊>The FASEB Journal >Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone
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Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone

机译：癌细胞中的核单体整联蛋白αv是由甲状腺激素调节的共觉器

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Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αvβ3. We investigated the role of thyroid hormone-induced internalization of nuclear integrin αv monomer. Physiological concentration of thyroxine (free T4, 10?10 M), but not 3,5,3′-triiodo-l-thyronine (T3), induced cellular internalization and nuclear translocation of integrin αv monomer in human non-small-cell lung cancer (H522) and ovarian carcinoma (OVCAR-3) cells. T4 did not complex with integrin αv monomer during its internalization. The αv monomer was phosphorylated by activated ERK1/2 when it heterodimerized with integrin β3 in vitro. Nuclear αv complexed with transcriptional coactivator proteins, p300 and STAT1, and with corepressor proteins, NCoR and SMRT. Nuclear αv monomer in T4-exposed cells, but not integrin β3, bound to promoters of specific genes that have important roles in cancer cells, including estrogen receptor-α, cyclooxygenase-2, hypoxia-inducible factor-1α, and thyroid hormone receptor β1 in chromatin immunoprecipitation assay. In summary, monomeric αv is a novel coactivator regulated from the cell surface by thyroid hormone for the expression of genes involved in tumorigenesis and angiogenesis. This study also offers a mechanism for modulation of gene expression by thyroid hormone that is adjunctive to the nuclear hormone receptor (TR)-T3 pathway.—Lin, H.-Y., Su, Y.-F., Hsieh, M.-T., Lin, S., Meng, M., London, D., Lin, C., Tang, H.-Y., Hwang, J., Davis, F. B., Mousa, S. A., and Davis, P. J. Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone.
机译：甲状腺激素通过杂细胞表面受体诱导肿瘤细胞和血管细胞增殖αvβ3。我们调查了甲状腺激素诱导的核整合蛋白αv单体内化的作用。甲状腺素的生理浓度（免费T4,10？10米），但不是3,5,3'-Triodo-L-炔酮（T3），诱导人类非小细胞肺中整合蛋白αv单体的细胞内化和核易位癌症（H522）和卵巢癌（OVCAR-3）细胞。在内化期间，T4与整合素αv单体没有复杂。当其在体外与整联蛋白β3杂化时，αv单体通过活化的ERK1 / 2磷酸化。核αv与转录共粘膜蛋白，p300和stat1复合，以及核心蛋白，ncor和smrt。 T4暴露细胞中的核αv单体，但不整合β3，与癌细胞中具有重要作用的特定基因的启动子，包括雌激素受体-α，环氧化酶-2，缺氧诱导因子-1α和甲状腺激素受体β1在染色质免疫沉淀测定中。总之，单体αv是由甲状腺激素从细胞表面调节的新型共觉器，用于表达肿瘤发生和血管生成的基因。本研究还提供了一种用于调节甲状腺激素的基因表达的机制，该甲状腺激素是核激素受体（TR）-T3途径.-林，H.- Y.，Su，Y.-f.，Hsieh，M。 -t。，林，S.，孟，M.，伦敦，D.，林，C.，唐，H.-Y.，Hwang，J.，Davis，FB，Mousa，SA和Davis，PJ核癌细胞中的单体整合蛋白αv是由甲状腺激素调节的共觉器。

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