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Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation

Most studies of Wnt signaling in malignant tissues have focused on the canonical Wnt pathway (CWP) due to its role in stimulating cellular proliferation. The role of the non-canonical Wnt pathway (NCWP) in tissues with dysregulated Wnt signaling is not fully understood. Understanding NCWP’s role is...

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Detalles Bibliográficos
Autores principales: Ali, Irshad, Medegan, Bani, Braun, Donald P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848951/
https://www.ncbi.nlm.nih.gov/pubmed/27049382
http://dx.doi.org/10.3390/ijms17040495
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author Ali, Irshad
Medegan, Bani
Braun, Donald P.
author_facet Ali, Irshad
Medegan, Bani
Braun, Donald P.
author_sort Ali, Irshad
collection PubMed
description Most studies of Wnt signaling in malignant tissues have focused on the canonical Wnt pathway (CWP) due to its role in stimulating cellular proliferation. The role of the non-canonical Wnt pathway (NCWP) in tissues with dysregulated Wnt signaling is not fully understood. Understanding NCWP’s role is important since these opposing pathways act in concert to maintain homeostasis in healthy tissues. Our preliminary studies demonstrated that LiCl inhibited proliferation of primary cells derived from colorectal cancer (CRC). Since LiCl stimulates cell proliferation in normal tissues and NCWP suppresses it, the present study was designed to investigate the impact of NCWP components in LiCl-mediated effects. LiCl-mediated inhibition of CRC cell proliferation (p < 0.001) and increased apoptosis (p < 0.01) coincided with 23-fold increase (p < 0.025) in the expression of the NCWP ligand, Wnt9A. LiCl also suppressed β-catenin mRNA (p < 0.03), total β-catenin protein (p < 0.025) and the active form of β-catenin. LiCl-mediated inhibition of CRC cell proliferation was partially reversed by IWP-2, and Wnt9A antibody. Recombinant Wnt9A protein emulated LiCl effects by suppressing β-catenin protein (p < 0.001), inhibiting proliferation (p < 0.001) and increasing apoptosis (p < 0.03). This is the first study to demonstrate induction of a NCWP ligand, Wnt9A as part of a mechanism for LiCl-mediated suppression of CRC cell proliferation.
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spelling pubmed-48489512016-05-04 Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation Ali, Irshad Medegan, Bani Braun, Donald P. Int J Mol Sci Article Most studies of Wnt signaling in malignant tissues have focused on the canonical Wnt pathway (CWP) due to its role in stimulating cellular proliferation. The role of the non-canonical Wnt pathway (NCWP) in tissues with dysregulated Wnt signaling is not fully understood. Understanding NCWP’s role is important since these opposing pathways act in concert to maintain homeostasis in healthy tissues. Our preliminary studies demonstrated that LiCl inhibited proliferation of primary cells derived from colorectal cancer (CRC). Since LiCl stimulates cell proliferation in normal tissues and NCWP suppresses it, the present study was designed to investigate the impact of NCWP components in LiCl-mediated effects. LiCl-mediated inhibition of CRC cell proliferation (p < 0.001) and increased apoptosis (p < 0.01) coincided with 23-fold increase (p < 0.025) in the expression of the NCWP ligand, Wnt9A. LiCl also suppressed β-catenin mRNA (p < 0.03), total β-catenin protein (p < 0.025) and the active form of β-catenin. LiCl-mediated inhibition of CRC cell proliferation was partially reversed by IWP-2, and Wnt9A antibody. Recombinant Wnt9A protein emulated LiCl effects by suppressing β-catenin protein (p < 0.001), inhibiting proliferation (p < 0.001) and increasing apoptosis (p < 0.03). This is the first study to demonstrate induction of a NCWP ligand, Wnt9A as part of a mechanism for LiCl-mediated suppression of CRC cell proliferation. MDPI 2016-04-02 /pmc/articles/PMC4848951/ /pubmed/27049382 http://dx.doi.org/10.3390/ijms17040495 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ali, Irshad
Medegan, Bani
Braun, Donald P.
Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation
title Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation
title_full Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation
title_fullStr Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation
title_full_unstemmed Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation
title_short Wnt9A Induction Linked to Suppression of Human Colorectal Cancer Cell Proliferation
title_sort wnt9a induction linked to suppression of human colorectal cancer cell proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848951/
https://www.ncbi.nlm.nih.gov/pubmed/27049382
http://dx.doi.org/10.3390/ijms17040495
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