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KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer

APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both β-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeti...

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Autores principales: Cho, Yong-Hee, Cha, Pu-Hyeon, Kaduwal, Saluja, Park, Jong-Chan, Lee, Sang-Kyu, Yoon, Jeong-Soo, Shin, Wookjin, Kim, Hyuntae, Ro, Eun Ji, Koo, Kyung-Hwa, Park, Ki-Sook, Han, Gyoonhee, Choi, Kang-Yell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348425/
https://www.ncbi.nlm.nih.gov/pubmed/27835580
http://dx.doi.org/10.18632/oncotarget.13172
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author Cho, Yong-Hee
Cha, Pu-Hyeon
Kaduwal, Saluja
Park, Jong-Chan
Lee, Sang-Kyu
Yoon, Jeong-Soo
Shin, Wookjin
Kim, Hyuntae
Ro, Eun Ji
Koo, Kyung-Hwa
Park, Ki-Sook
Han, Gyoonhee
Choi, Kang-Yell
author_facet Cho, Yong-Hee
Cha, Pu-Hyeon
Kaduwal, Saluja
Park, Jong-Chan
Lee, Sang-Kyu
Yoon, Jeong-Soo
Shin, Wookjin
Kim, Hyuntae
Ro, Eun Ji
Koo, Kyung-Hwa
Park, Ki-Sook
Han, Gyoonhee
Choi, Kang-Yell
author_sort Cho, Yong-Hee
collection PubMed
description APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both β-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeting both the Wnt/β-catenin and Ras pathways could be an ideal therapeutic approach for treating mCRC patients. In this study, we characterized the roles of KY1022, a small molecule that destabilizes both β-catenin and Ras via targeting the Wnt/β-catenin pathway, in inhibiting the cellular events, including EMT, an initial process of metastasis, and apoptosis. As shown by in vitro and in vivo studies using APC(Min/+)/K-Ras(G12D)LA2 mice, KY1022 effectively suppressed the development of mCRC at an early stage of tumorigenesis. A small molecular approach degrading both β-catenin and Ras via inhibition of the Wnt/β-catenin signaling would be an ideal strategy for treatment of mCRC.
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spelling pubmed-53484252017-03-31 KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer Cho, Yong-Hee Cha, Pu-Hyeon Kaduwal, Saluja Park, Jong-Chan Lee, Sang-Kyu Yoon, Jeong-Soo Shin, Wookjin Kim, Hyuntae Ro, Eun Ji Koo, Kyung-Hwa Park, Ki-Sook Han, Gyoonhee Choi, Kang-Yell Oncotarget Research Paper APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both β-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeting both the Wnt/β-catenin and Ras pathways could be an ideal therapeutic approach for treating mCRC patients. In this study, we characterized the roles of KY1022, a small molecule that destabilizes both β-catenin and Ras via targeting the Wnt/β-catenin pathway, in inhibiting the cellular events, including EMT, an initial process of metastasis, and apoptosis. As shown by in vitro and in vivo studies using APC(Min/+)/K-Ras(G12D)LA2 mice, KY1022 effectively suppressed the development of mCRC at an early stage of tumorigenesis. A small molecular approach degrading both β-catenin and Ras via inhibition of the Wnt/β-catenin signaling would be an ideal strategy for treatment of mCRC. Impact Journals LLC 2016-11-07 /pmc/articles/PMC5348425/ /pubmed/27835580 http://dx.doi.org/10.18632/oncotarget.13172 Text en Copyright: © 2016 Cho et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cho, Yong-Hee
Cha, Pu-Hyeon
Kaduwal, Saluja
Park, Jong-Chan
Lee, Sang-Kyu
Yoon, Jeong-Soo
Shin, Wookjin
Kim, Hyuntae
Ro, Eun Ji
Koo, Kyung-Hwa
Park, Ki-Sook
Han, Gyoonhee
Choi, Kang-Yell
KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
title KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
title_full KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
title_fullStr KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
title_full_unstemmed KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
title_short KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
title_sort ky1022, a small molecule destabilizing ras via targeting the wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348425/
https://www.ncbi.nlm.nih.gov/pubmed/27835580
http://dx.doi.org/10.18632/oncotarget.13172
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