Crosstalk between integrin αvβ3 and ERα contributes to thyroid hormone-induced proliferation of ovarian cancer cells

Meng Ti Hsieh, Le Ming Wang, Chun A. Changou, Yu Tang Chin, Yu Chen S.H. Yang, Hsuan Yu Lai, Sheng Yang Lee, Yung Ning Yang, Jacqueline Whang-Peng, Leroy F. Liu, Hung Yun Lin, Shaker A. Mousa, Paul J. Davis

研究成果: 雜誌貢獻文章

15 引文 (Scopus)

摘要

Ovarian cancer is the leading cause of death in gynecological diseases. Thyroid hormone promotes proliferation of ovarian cancer cells via cell surface receptor integrin αvβ3 that activates extracellular regulated kinase (ERK1/2). However, the mechanisms are still not fully understood. Thyroxine (T4) at a physiologic total hormone concentration (10-7 M) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T3) at a supraphysiologic concentration. Thyroid hormone (T4 and T3) treatment of human ovarian cancer cells resulted in enhanced activation of the Ras/MAPK(ERK1/2) signal transduction pathway. An MEK inhibitor (PD98059) blocked hormone-induced cell proliferation but not ER phosphorylation. Knock-down of either integrin αv or β3 by RNAi blocked thyroid hormone-induced phosphorylation of ERK1/2. We also found that thyroid hormone causes elevated phosphorylation and nuclear enrichment of estrogen receptor a (ERa). Confocal microscopy indicated that both T4 and estradiol (E2) caused nuclear translocation of integrin αv and phosphorylation of ERα. The specific ERa antagonist (ICI 182,780; fulvestrant) blocked T4-induced ERK1/2 activation, ERa phosphorylation, PCNA expression and proliferation. The nuclear co-localization of integrin αv and phosphorylated ERa was inhibited by ICI. ICI time-course studies indicated that mechanisms involved in T4- and E2-induced nuclear co-localization of phosphorylated ERa and integrin αv are dissimilar. Chromatin immunoprecipitation results showed that T4-induced binding of integrin αv monomer to ERa promoter and this was reduced by ICI. In summary, thyroid hormone stimulates proliferation of ovarian cancer cells via crosstalk between integrin αv and ERα, mimicking functions of E2.
原文英語
頁(從 - 到)24237-24249
頁數13
期刊Oncotarget
8
發行號15
DOIs
出版狀態已發佈 - 2017

指紋

Thyroid Hormones
Integrins
Ovarian Neoplasms
Estrogen Receptors
Phosphorylation
Proliferating Cell Nuclear Antigen
Thyroxine
Thyronines
Hormones
Mitogen-Activated Protein Kinase 3
Chromatin Immunoprecipitation
Mitogen-Activated Protein Kinase Kinases
Cell Surface Receptors
Triiodothyronine
RNA Interference
Confocal Microscopy
Cause of Death
Estradiol
Signal Transduction
Cell Proliferation

ASJC Scopus subject areas

  • Oncology

引用此文

Crosstalk between integrin αvβ3 and ERα contributes to thyroid hormone-induced proliferation of ovarian cancer cells. / Hsieh, Meng Ti; Wang, Le Ming; Changou, Chun A.; Chin, Yu Tang; Yang, Yu Chen S.H.; Lai, Hsuan Yu; Lee, Sheng Yang; Yang, Yung Ning; Whang-Peng, Jacqueline; Liu, Leroy F.; Lin, Hung Yun; Mousa, Shaker A.; Davis, Paul J.

於: Oncotarget, 卷 8, 編號 15, 2017, p. 24237-24249.

研究成果: 雜誌貢獻文章

Hsieh, Meng Ti ; Wang, Le Ming ; Changou, Chun A. ; Chin, Yu Tang ; Yang, Yu Chen S.H. ; Lai, Hsuan Yu ; Lee, Sheng Yang ; Yang, Yung Ning ; Whang-Peng, Jacqueline ; Liu, Leroy F. ; Lin, Hung Yun ; Mousa, Shaker A. ; Davis, Paul J. / Crosstalk between integrin αvβ3 and ERα contributes to thyroid hormone-induced proliferation of ovarian cancer cells. 於: Oncotarget. 2017 ; 卷 8, 編號 15. 頁 24237-24249.
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abstract = "Ovarian cancer is the leading cause of death in gynecological diseases. Thyroid hormone promotes proliferation of ovarian cancer cells via cell surface receptor integrin αvβ3 that activates extracellular regulated kinase (ERK1/2). However, the mechanisms are still not fully understood. Thyroxine (T4) at a physiologic total hormone concentration (10-7 M) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T3) at a supraphysiologic concentration. Thyroid hormone (T4 and T3) treatment of human ovarian cancer cells resulted in enhanced activation of the Ras/MAPK(ERK1/2) signal transduction pathway. An MEK inhibitor (PD98059) blocked hormone-induced cell proliferation but not ER phosphorylation. Knock-down of either integrin αv or β3 by RNAi blocked thyroid hormone-induced phosphorylation of ERK1/2. We also found that thyroid hormone causes elevated phosphorylation and nuclear enrichment of estrogen receptor a (ERa). Confocal microscopy indicated that both T4 and estradiol (E2) caused nuclear translocation of integrin αv and phosphorylation of ERα. The specific ERa antagonist (ICI 182,780; fulvestrant) blocked T4-induced ERK1/2 activation, ERa phosphorylation, PCNA expression and proliferation. The nuclear co-localization of integrin αv and phosphorylated ERa was inhibited by ICI. ICI time-course studies indicated that mechanisms involved in T4- and E2-induced nuclear co-localization of phosphorylated ERa and integrin αv are dissimilar. Chromatin immunoprecipitation results showed that T4-induced binding of integrin αv monomer to ERa promoter and this was reduced by ICI. In summary, thyroid hormone stimulates proliferation of ovarian cancer cells via crosstalk between integrin αv and ERα, mimicking functions of E2.",
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AU - Wang, Le Ming

AU - Changou, Chun A.

AU - Chin, Yu Tang

AU - Yang, Yu Chen S.H.

AU - Lai, Hsuan Yu

AU - Lee, Sheng Yang

AU - Yang, Yung Ning

AU - Whang-Peng, Jacqueline

AU - Liu, Leroy F.

AU - Lin, Hung Yun

AU - Mousa, Shaker A.

AU - Davis, Paul J.

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AB - Ovarian cancer is the leading cause of death in gynecological diseases. Thyroid hormone promotes proliferation of ovarian cancer cells via cell surface receptor integrin αvβ3 that activates extracellular regulated kinase (ERK1/2). However, the mechanisms are still not fully understood. Thyroxine (T4) at a physiologic total hormone concentration (10-7 M) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T3) at a supraphysiologic concentration. Thyroid hormone (T4 and T3) treatment of human ovarian cancer cells resulted in enhanced activation of the Ras/MAPK(ERK1/2) signal transduction pathway. An MEK inhibitor (PD98059) blocked hormone-induced cell proliferation but not ER phosphorylation. Knock-down of either integrin αv or β3 by RNAi blocked thyroid hormone-induced phosphorylation of ERK1/2. We also found that thyroid hormone causes elevated phosphorylation and nuclear enrichment of estrogen receptor a (ERa). Confocal microscopy indicated that both T4 and estradiol (E2) caused nuclear translocation of integrin αv and phosphorylation of ERα. The specific ERa antagonist (ICI 182,780; fulvestrant) blocked T4-induced ERK1/2 activation, ERa phosphorylation, PCNA expression and proliferation. The nuclear co-localization of integrin αv and phosphorylated ERa was inhibited by ICI. ICI time-course studies indicated that mechanisms involved in T4- and E2-induced nuclear co-localization of phosphorylated ERa and integrin αv are dissimilar. Chromatin immunoprecipitation results showed that T4-induced binding of integrin αv monomer to ERa promoter and this was reduced by ICI. In summary, thyroid hormone stimulates proliferation of ovarian cancer cells via crosstalk between integrin αv and ERα, mimicking functions of E2.

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KW - Ovarian cancer

KW - Thyroid hormone

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