PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.

Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was required for the proliferation of transform...

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Autores principales:	Tracy M Covey, Simran Kaur, Tina Tan Ong, Kyle D Proffitt, Yonghui Wu, Patrick Tan, David M Virshup
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d803ceca73949ce8406e72b0add2d83
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spelling	oai:doaj.org-article:6d803ceca73949ce8406e72b0add2d832021-11-18T07:22:39ZPORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.1932-620310.1371/journal.pone.0034532https://doaj.org/article/6d803ceca73949ce8406e72b0add2d832012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22509316/?tool=EBIhttps://doaj.org/toc/1932-6203Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was required for the proliferation of transformed cells. Knockdown of PORCN by multiple independent siRNAs results in a cell growth defect in a subset of epithelial cancer cell lines. The growth defect is transformation-dependent in human mammary epithelial (HMEC) cells. Additionally, inducible PORCN knockdown by two independent shRNAs markedly reduces the growth of established MDA-MB-231 cancers in orthotopic xenografts in immunodeficient mice. Unexpectedly, the proliferation defect resulting from loss of PORCN occurs in a Wnt-independent manner, as it is rescued by re-expression of catalytically inactive PORCN, and is not seen after RNAi-mediated knockdown of the Wnt carrier protein WLS, nor after treatment with the PORCN inhibitor IWP. Consistent with a role in a Wnt-independent pathway, knockdown of PORCN regulates a distinct set of genes that are not altered by other inhibitors of Wnt signaling. PORCN protein thus appears to moonlight in a novel signaling pathway that is rate-limiting for cancer cell growth and tumorigenesis independent of its enzymatic function in Wnt biosynthesis and secretion.Tracy M CoveySimran KaurTina Tan OngKyle D ProffittYonghui WuPatrick TanDavid M VirshupPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34532 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tracy M Covey Simran Kaur Tina Tan Ong Kyle D Proffitt Yonghui Wu Patrick Tan David M Virshup PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.
description	Porcupine (PORCN) is a membrane-bound O-acyl transferase that is required for the palmitoylation of Wnt proteins, and that is essential in diverse Wnt pathways for Wnt-Wntless (WLS) binding, Wnt secretion, and Wnt signaling activity. We tested if PORCN was required for the proliferation of transformed cells. Knockdown of PORCN by multiple independent siRNAs results in a cell growth defect in a subset of epithelial cancer cell lines. The growth defect is transformation-dependent in human mammary epithelial (HMEC) cells. Additionally, inducible PORCN knockdown by two independent shRNAs markedly reduces the growth of established MDA-MB-231 cancers in orthotopic xenografts in immunodeficient mice. Unexpectedly, the proliferation defect resulting from loss of PORCN occurs in a Wnt-independent manner, as it is rescued by re-expression of catalytically inactive PORCN, and is not seen after RNAi-mediated knockdown of the Wnt carrier protein WLS, nor after treatment with the PORCN inhibitor IWP. Consistent with a role in a Wnt-independent pathway, knockdown of PORCN regulates a distinct set of genes that are not altered by other inhibitors of Wnt signaling. PORCN protein thus appears to moonlight in a novel signaling pathway that is rate-limiting for cancer cell growth and tumorigenesis independent of its enzymatic function in Wnt biosynthesis and secretion.
format	article
author	Tracy M Covey Simran Kaur Tina Tan Ong Kyle D Proffitt Yonghui Wu Patrick Tan David M Virshup
author_facet	Tracy M Covey Simran Kaur Tina Tan Ong Kyle D Proffitt Yonghui Wu Patrick Tan David M Virshup
author_sort	Tracy M Covey
title	PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.
title_short	PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.
title_full	PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.
title_fullStr	PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.
title_full_unstemmed	PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.
title_sort	porcn moonlights in a wnt-independent pathway that regulates cancer cell proliferation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6d803ceca73949ce8406e72b0add2d83
work_keys_str_mv	AT tracymcovey porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation AT simrankaur porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation AT tinatanong porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation AT kyledproffitt porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation AT yonghuiwu porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation AT patricktan porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation AT davidmvirshup porcnmoonlightsinawntindependentpathwaythatregulatescancercellproliferation
_version_	1718423538362220544

PORCN moonlights in a Wnt-independent pathway that regulates cancer cell proliferation.

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