VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer

Abstract Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the b...

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Autores principales:	Yinglong Zhang, He Shen, Henry G. Withers, Nuo Yang, Kayla E. Denson, Ashley L. Mussell, Alexander Truskinovsky, Qingyu Fan, Irwin H. Gelman, Costa Frangou, Jianmin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e5cb097cea444e6e89789de7e2797e41
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spelling	oai:doaj.org-article:e5cb097cea444e6e89789de7e2797e412021-12-02T11:41:12ZVGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer10.1038/s41598-017-06227-72045-2322https://doaj.org/article/e5cb097cea444e6e89789de7e2797e412017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06227-7https://doaj.org/toc/2045-2322Abstract Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown. Here, we report that diminished VGLL4 expression, but not VGLL1-3, correlated with both shorter relapse-free survival and shorter disease-specific survival of cancer patients with different molecular subtypes of breast cancer. Additionally, we further demonstrate that overexpression of VGLL4 reduces breast cancer cell proliferation, migration, intravasation/extravasation potential, favors cell death, and suppresses tumor growth in vivo. Mechanistically, VGLL4 negatively regulates the TEAD1-YAP1 transcriptional complex and exerts its growth inhibitory control through its evolutionary conserved TDU2 domain at its C-terminus. The results suggest that VGLL4 is a candidate tumor suppressor gene which acts by selectively antagonizing YAP-dependent tumor growth. VGLL4 may be a promising therapeutic target in breast cancer.Yinglong ZhangHe ShenHenry G. WithersNuo YangKayla E. DensonAshley L. MussellAlexander TruskinovskyQingyu FanIrwin H. GelmanCosta FrangouJianmin ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yinglong Zhang He Shen Henry G. Withers Nuo Yang Kayla E. Denson Ashley L. Mussell Alexander Truskinovsky Qingyu Fan Irwin H. Gelman Costa Frangou Jianmin Zhang VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer
description	Abstract Members of the mammalian Vestigial-like (VGLL) family of transcriptional cofactors activate genes in response to a wide variety of environmental cues. Recently, VGLL proteins have been proposed to regulate key signaling networks involved in cancer development and progression. However, the biological and clinical significance of VGLL dysregulation in human breast cancer pathogenesis remains unknown. Here, we report that diminished VGLL4 expression, but not VGLL1-3, correlated with both shorter relapse-free survival and shorter disease-specific survival of cancer patients with different molecular subtypes of breast cancer. Additionally, we further demonstrate that overexpression of VGLL4 reduces breast cancer cell proliferation, migration, intravasation/extravasation potential, favors cell death, and suppresses tumor growth in vivo. Mechanistically, VGLL4 negatively regulates the TEAD1-YAP1 transcriptional complex and exerts its growth inhibitory control through its evolutionary conserved TDU2 domain at its C-terminus. The results suggest that VGLL4 is a candidate tumor suppressor gene which acts by selectively antagonizing YAP-dependent tumor growth. VGLL4 may be a promising therapeutic target in breast cancer.
format	article
author	Yinglong Zhang He Shen Henry G. Withers Nuo Yang Kayla E. Denson Ashley L. Mussell Alexander Truskinovsky Qingyu Fan Irwin H. Gelman Costa Frangou Jianmin Zhang
author_facet	Yinglong Zhang He Shen Henry G. Withers Nuo Yang Kayla E. Denson Ashley L. Mussell Alexander Truskinovsky Qingyu Fan Irwin H. Gelman Costa Frangou Jianmin Zhang
author_sort	Yinglong Zhang
title	VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer
title_short	VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer
title_full	VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer
title_fullStr	VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer
title_full_unstemmed	VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer
title_sort	vgll4 selectively represses yap-dependent gene induction and tumorigenic phenotypes in breast cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e5cb097cea444e6e89789de7e2797e41
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VGLL4 Selectively Represses YAP-Dependent Gene Induction and Tumorigenic Phenotypes in Breast Cancer

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