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Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone
Author(s) -
Lin HungYun,
Su YeeFun,
Hsieh MengTi,
Lin Sharon,
Meng Ran,
London David,
Lin Cassie,
Tang HengYuan,
Hwang Jaulang,
Davis Faith B.,
Mousa Shaker A.,
Davis Paul J.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-227132
Subject(s) - thyroid hormone receptor , nuclear receptor , thyroid hormone receptor beta , coactivator , internalization , thyroid hormone receptor alpha , chemistry , cancer research , microbiology and biotechnology , biology , hormone receptor , medicine , receptor , biochemistry , transcription factor , cancer , gene , breast cancer
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 T 4 , 10 –10 M), but not 3,5,3'‐triiodo‐L‐thyronine (T 3 ), induced cellular internalization and nuclear translocation of integrin αv monomer in human non‐small‐cell lung cancer (H522) and ovarian carcinoma (OVCAR‐3) cells. T 4 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 T 4 ‐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)‐T 3 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. FASEB J. 27, 3209–3216 (2013). www.fasebj.org