Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines

Tumor repopulation after radiotherapy is a big obstacle for clinical cancer therapy. The molecular mechanisms of tumor cell repopulation after radiotherapy remain unclear. This study investigated the role of sonic hedgehog (SHH) and Wnt signaling pathways in tumor repopulation after radiotherapy in...

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Main Authors:	Ma, Jingjing, Cheng, Jin, Gong, Yanping, Tian, Ling, Huang, Qian
Format:	Online
Language:	English
Published:	The Company of Biologists Limited 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381337/

id	pubmed-4381337
recordtype	oai_dc
spelling	pubmed-43813372015-04-15 Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines Ma, Jingjing Cheng, Jin Gong, Yanping Tian, Ling Huang, Qian Research Article Tumor repopulation after radiotherapy is a big obstacle for clinical cancer therapy. The molecular mechanisms of tumor cell repopulation after radiotherapy remain unclear. This study investigated the role of sonic hedgehog (SHH) and Wnt signaling pathways in tumor repopulation after radiotherapy in an in vitro repopulation model. In this model, irradiated dying tumor cells functioned as feeder cells, whereas luciferase-labeled living tumor cells acted as reporter cells. Proliferation of reporter cells was measured by bioluminescence imaging. Results showed that irradiated dying HT29 and Panc1 tumor cells significantly stimulated the repopulation of living cells in their respective cultures. In HT29 and Panc1 cells, radiation significantly inhibited Wnt activity. In the irradiated dying HT29 and Panc1 cells, the level of the activated nuclear β-catenin was significantly decreased. Treatment with the Wnt agonist 68166 significantly decreased, whereas treatment with Wnt antagonist significantly increased, repopulation in HT29 and Panc1 tumor cells in a dose-dependent manner. β-catenin short-hairpin RNA (shRNA) also significantly promoted tumor cell repopulation. The level of secreted frizzled related protein-1 (SFRP1), hedgehog and Gli1 were increased in irradiated cells. Our results highlight the interaction between Wnt and SHH signaling pathways in dying tumor cells and suggest that downregulation of Wnt signaling after SHH activation is negatively associated with tumor repopulation. The Company of Biologists Limited 2015-04 2015-02-20 /pmc/articles/PMC4381337/ /pubmed/25713298 http://dx.doi.org/10.1242/dmm.018887 Text en © 2015. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ma, Jingjing Cheng, Jin Gong, Yanping Tian, Ling Huang, Qian
spellingShingle	Ma, Jingjing Cheng, Jin Gong, Yanping Tian, Ling Huang, Qian Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
author_facet	Ma, Jingjing Cheng, Jin Gong, Yanping Tian, Ling Huang, Qian
author_sort	Ma, Jingjing
title	Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
title_short	Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
title_full	Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
title_fullStr	Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
title_full_unstemmed	Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
title_sort	downregulation of wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines
description	Tumor repopulation after radiotherapy is a big obstacle for clinical cancer therapy. The molecular mechanisms of tumor cell repopulation after radiotherapy remain unclear. This study investigated the role of sonic hedgehog (SHH) and Wnt signaling pathways in tumor repopulation after radiotherapy in an in vitro repopulation model. In this model, irradiated dying tumor cells functioned as feeder cells, whereas luciferase-labeled living tumor cells acted as reporter cells. Proliferation of reporter cells was measured by bioluminescence imaging. Results showed that irradiated dying HT29 and Panc1 tumor cells significantly stimulated the repopulation of living cells in their respective cultures. In HT29 and Panc1 cells, radiation significantly inhibited Wnt activity. In the irradiated dying HT29 and Panc1 cells, the level of the activated nuclear β-catenin was significantly decreased. Treatment with the Wnt agonist 68166 significantly decreased, whereas treatment with Wnt antagonist significantly increased, repopulation in HT29 and Panc1 tumor cells in a dose-dependent manner. β-catenin short-hairpin RNA (shRNA) also significantly promoted tumor cell repopulation. The level of secreted frizzled related protein-1 (SFRP1), hedgehog and Gli1 were increased in irradiated cells. Our results highlight the interaction between Wnt and SHH signaling pathways in dying tumor cells and suggest that downregulation of Wnt signaling after SHH activation is negatively associated with tumor repopulation.
publisher	The Company of Biologists Limited
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381337/
_version_	1613206161239048192

Downregulation of Wnt signaling by sonic hedgehog activation promotes repopulation of human tumor cell lines

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