Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0034532
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
Citation: 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. https://doi.org/10.1371/journal.pone.0034532
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
URI: http://scholarbank.nus.edu.sg/handle/10635/110216
ISSN: 19326203
DOI: 10.1371/journal.pone.0034532
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