Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone

Hung Yun Lin, Yee Fun Su, Meng Ti Hsieh, Sharon Lin, Ran Meng, David London, Cassie Lin, Heng Yuan Tang, Jaulang Hwang, Faith B. Davis, Shaker A. Mousa, Paul J. Davis

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αv β3. 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 v 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 α1 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.

Original languageEnglish
Pages (from-to)3209-3216
Number of pages8
JournalFASEB Journal
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Thyroid Hormones
Integrins
Cells
Monomers
Neoplasms
Genes
Thyronines
STAT1 Transcription Factor
CD4-Positive T-Lymphocytes
Gene Expression
Hypoxia-Inducible Factor 1
Thyroid Hormone Receptors
Co-Repressor Proteins
Estrogen Receptor beta
Chromatin Immunoprecipitation
Blood vessels
Cell proliferation
Cell Surface Receptors
Cyclooxygenase 2
Cytoplasmic and Nuclear Receptors

Keywords

  • Angiogenesis
  • Carcinogenesis
  • Gene expression
  • Thyroxine

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Lin, H. Y., Su, Y. F., Hsieh, M. T., Lin, S., Meng, R., London, D., ... Davis, P. J. (2013). Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone. FASEB Journal, 27(8), 3209-3216. https://doi.org/10.1096/fj.12-227132

Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone. / Lin, Hung Yun; Su, Yee Fun; Hsieh, Meng Ti; Lin, Sharon; Meng, Ran; London, David; Lin, Cassie; Tang, Heng Yuan; Hwang, Jaulang; Davis, Faith B.; Mousa, Shaker A.; Davis, Paul J.

In: FASEB Journal, Vol. 27, No. 8, 08.2013, p. 3209-3216.

Research output: Contribution to journalArticle

Lin, HY, Su, YF, Hsieh, MT, Lin, S, Meng, R, London, D, Lin, C, Tang, HY, Hwang, J, Davis, FB, Mousa, SA & Davis, PJ 2013, 'Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone', FASEB Journal, vol. 27, no. 8, pp. 3209-3216. https://doi.org/10.1096/fj.12-227132
Lin, Hung Yun ; Su, Yee Fun ; Hsieh, Meng Ti ; Lin, Sharon ; Meng, Ran ; London, David ; Lin, Cassie ; Tang, Heng Yuan ; Hwang, Jaulang ; Davis, Faith B. ; Mousa, Shaker A. ; Davis, Paul J. / Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone. In: FASEB Journal. 2013 ; Vol. 27, No. 8. pp. 3209-3216.
@article{aaf642b15f134e20b826dae53af45bae,
title = "Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone",
abstract = "Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αv β3. 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 v 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 α1 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.",
keywords = "Angiogenesis, Carcinogenesis, Gene expression, Thyroxine",
author = "Lin, {Hung Yun} and Su, {Yee Fun} and Hsieh, {Meng Ti} and Sharon Lin and Ran Meng and David London and Cassie Lin and Tang, {Heng Yuan} and Jaulang Hwang and Davis, {Faith B.} and Mousa, {Shaker A.} and Davis, {Paul J.}",
year = "2013",
month = "8",
doi = "10.1096/fj.12-227132",
language = "English",
volume = "27",
pages = "3209--3216",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "8",

}

TY - JOUR

T1 - Nuclear monomeric integrin αv in cancer cells is a coactivator regulated by thyroid hormone

AU - Lin, Hung Yun

AU - Su, Yee Fun

AU - Hsieh, Meng Ti

AU - Lin, Sharon

AU - Meng, Ran

AU - London, David

AU - Lin, Cassie

AU - Tang, Heng Yuan

AU - Hwang, Jaulang

AU - Davis, Faith B.

AU - Mousa, Shaker A.

AU - Davis, Paul J.

PY - 2013/8

Y1 - 2013/8

N2 - Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αv β3. 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 v 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 α1 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.

AB - Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αv β3. 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 v 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 α1 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.

KW - Angiogenesis

KW - Carcinogenesis

KW - Gene expression

KW - Thyroxine

UR - http://www.scopus.com/inward/record.url?scp=84881171782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881171782&partnerID=8YFLogxK

U2 - 10.1096/fj.12-227132

DO - 10.1096/fj.12-227132

M3 - Article

C2 - 23640055

AN - SCOPUS:84881171782

VL - 27

SP - 3209

EP - 3216

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 8

ER -