Please use this identifier to cite or link to this item:
Title: PORCN moonlights in a wnt-independent pathway that regulates cancer cell proliferation
Authors: Covey, T.M.
Kaur, S.
Ong, T.
Proffitt, K.D.
Wu, Y.
Tan, P. 
Virshup, D.M.
Issue Date: 2012
Source: Covey, T.M., Kaur, S., Ong, T., Proffitt, K.D., Wu, Y., Tan, P., Virshup, D.M. (2012). PORCN moonlights in a wnt-independent pathway that regulates cancer cell proliferation. PLoS ONE 7 (4) : -. ScholarBank@NUS Repository.
Abstract: 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. © 2012 Covey et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0034532
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2012-PORCN_moonlights_wnt-independent_pathway_regulates-published.pdf1.77 MBAdobe PDF




checked on Mar 8, 2018


checked on Feb 7, 2018

Page view(s)

checked on Mar 12, 2018


checked on Mar 12, 2018

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.